58.
Gomez-Cabrero, D.; Abugessaisa, I.; Maier, D.; Teschendorff, A.; Merkenschlager, M.; Gisel, A.; Ballestar, E.; Bongcam-Rudloff, E.; Conesa, A.; Tegner, J.
Data integration in the era of omics: current and future challenges Journal Article
In: BMC SYSTEMS BIOLOGY, vol. 8, no. 2, 2014, ISSN: 1752-0509.
@article{ISI:000333681300001,
title = {Data integration in the era of omics: current and future challenges},
author = { D. Gomez-Cabrero and I. Abugessaisa and D. Maier and A. Teschendorff and M. Merkenschlager and A. Gisel and E. Ballestar and E. Bongcam-Rudloff and A. Conesa and J. Tegner},
url = {http://dx.doi.org/10.1186/1752-0509-8-S2-I1},
doi = {10.1186/1752-0509-8-S2-I1},
issn = {1752-0509},
year = {2014},
date = {2014-03-01},
journal = {BMC SYSTEMS BIOLOGY},
volume = {8},
number = {2},
abstract = {To integrate heterogeneous and large omics data constitutes not only a
conceptual challenge but a practical hurdle in the daily analysis of
omics data. With the rise of novel omics technologies and through
large-scale consortia projects, biological systems are being further
investigated at an unprecedented scale generating heterogeneous and
often large data sets. These data-sets encourage researchers to develop
novel data integration methodologies. In this introduction we review the
definition and characterize current efforts on data integration in the
life sciences. We have used a web-survey to assess current research
projects on data-integration to tap into the views, needs and challenges
as currently perceived by parts of the research community.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
To integrate heterogeneous and large omics data constitutes not only a
conceptual challenge but a practical hurdle in the daily analysis of
omics data. With the rise of novel omics technologies and through
large-scale consortia projects, biological systems are being further
investigated at an unprecedented scale generating heterogeneous and
often large data sets. These data-sets encourage researchers to develop
novel data integration methodologies. In this introduction we review the
definition and characterize current efforts on data integration in the
life sciences. We have used a web-survey to assess current research
projects on data-integration to tap into the views, needs and challenges
as currently perceived by parts of the research community.
conceptual challenge but a practical hurdle in the daily analysis of
omics data. With the rise of novel omics technologies and through
large-scale consortia projects, biological systems are being further
investigated at an unprecedented scale generating heterogeneous and
often large data sets. These data-sets encourage researchers to develop
novel data integration methodologies. In this introduction we review the
definition and characterize current efforts on data integration in the
life sciences. We have used a web-survey to assess current research
projects on data-integration to tap into the views, needs and challenges
as currently perceived by parts of the research community.
57.
Conesa, A.; Mortazavi, A.
The common ground of genomics and systems biology Journal Article
In: BMC SYSTEMS BIOLOGY, vol. 8, no. 2, 2014, ISSN: 1752-0509, (High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013).
@article{ISI:000333681300002,
title = {The common ground of genomics and systems biology},
author = { A. Conesa and A. Mortazavi},
url = {http://dx.doi.org/10.1186/1752-0509-8-S2-S1},
doi = {10.1186/1752-0509-8-S2-S1},
issn = {1752-0509},
year = {2014},
date = {2014-03-01},
journal = {BMC SYSTEMS BIOLOGY},
volume = {8},
number = {2},
abstract = {The rise of systems biology is intertwined with that of genomics, yet
their primordial relationship to one another is ill-defined. We discuss
how the growth of genomics provided a critical boost to the popularity
of systems biology. We describe the parts of genomics that share common
areas of interest with systems biology today in the areas of gene
expression, network inference, chromatin state analysis, pathway
analysis, personalized medicine, and upcoming areas of synergy as
genomics continues to expand its scope across all biomedical fields.},
note = {High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The rise of systems biology is intertwined with that of genomics, yet
their primordial relationship to one another is ill-defined. We discuss
how the growth of genomics provided a critical boost to the popularity
of systems biology. We describe the parts of genomics that share common
areas of interest with systems biology today in the areas of gene
expression, network inference, chromatin state analysis, pathway
analysis, personalized medicine, and upcoming areas of synergy as
genomics continues to expand its scope across all biomedical fields.
their primordial relationship to one another is ill-defined. We discuss
how the growth of genomics provided a critical boost to the popularity
of systems biology. We describe the parts of genomics that share common
areas of interest with systems biology today in the areas of gene
expression, network inference, chromatin state analysis, pathway
analysis, personalized medicine, and upcoming areas of synergy as
genomics continues to expand its scope across all biomedical fields.
56.
Ponzoni, I.; Nueda, M. J.; Tarazona, S.; Goetz, S.; Montaner, D.; Dussaut, J. S.; Dopazo, J.; Conesa, A.
Pathway network inference from gene expression data Journal Article
In: BMC SYSTEMS BIOLOGY, vol. 8, no. 2, 2014, ISSN: 1752-0509, (High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013).
@article{ISI:000333681300008,
title = {Pathway network inference from gene expression data},
author = { I. Ponzoni and M. J. Nueda and S. Tarazona and S. Goetz and D. Montaner and J. S. Dussaut and J. Dopazo and A. Conesa},
url = {http://dx.doi.org/10.1186/1752-0509-8-S2-S7},
doi = {10.1186/1752-0509-8-S2-S7},
issn = {1752-0509},
year = {2014},
date = {2014-03-01},
journal = {BMC SYSTEMS BIOLOGY},
volume = {8},
number = {2},
abstract = {Background: The development of high-throughput omics technologies
enabled genome-wide measurements of the activity of cellular elements
and provides the analytical resources for the progress of the Systems
Biology discipline. Analysis and interpretation of gene expression data
has evolved from the gene to the pathway and interaction level, i.e.
from the detection of differentially expressed genes, to the
establishment of gene interaction networks and the identification of
enriched functional categories. Still, the understanding of biological
systems requires a further level of analysis that addresses the
characterization of the interaction between functional modules.
Results: We present a novel computational methodology to study the
functional interconnections among the molecular elements of a biological
system. The PANA approach uses high-throughput genomics measurements and
a functional annotation scheme to extract an activity profile from each
functional block -or pathway-followed by machine-learning methods to
infer the relationships between these functional profiles. The result is
a global, interconnected network of pathways that represents the
functional cross-talk within the molecular system. We have applied this
approach to describe the functional transcriptional connections during
the yeast cell cycle and to identify pathways that change their
connectivity in a disease condition using an Alzheimer example.
Conclusions: PANA is a useful tool to deepen in our understanding of the
functional interdependences that operate within complex biological
systems. We show the approach is algorithmically consistent and the
inferred network is well supported by the available functional data. The
method allows the dissection of the molecular basis of the functional
connections and we describe the different regulatory mechanisms that
explain the network's topology obtained for the yeast cell cycle data.},
note = {High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: The development of high-throughput omics technologies
enabled genome-wide measurements of the activity of cellular elements
and provides the analytical resources for the progress of the Systems
Biology discipline. Analysis and interpretation of gene expression data
has evolved from the gene to the pathway and interaction level, i.e.
from the detection of differentially expressed genes, to the
establishment of gene interaction networks and the identification of
enriched functional categories. Still, the understanding of biological
systems requires a further level of analysis that addresses the
characterization of the interaction between functional modules.
Results: We present a novel computational methodology to study the
functional interconnections among the molecular elements of a biological
system. The PANA approach uses high-throughput genomics measurements and
a functional annotation scheme to extract an activity profile from each
functional block -or pathway-followed by machine-learning methods to
infer the relationships between these functional profiles. The result is
a global, interconnected network of pathways that represents the
functional cross-talk within the molecular system. We have applied this
approach to describe the functional transcriptional connections during
the yeast cell cycle and to identify pathways that change their
connectivity in a disease condition using an Alzheimer example.
Conclusions: PANA is a useful tool to deepen in our understanding of the
functional interdependences that operate within complex biological
systems. We show the approach is algorithmically consistent and the
inferred network is well supported by the available functional data. The
method allows the dissection of the molecular basis of the functional
connections and we describe the different regulatory mechanisms that
explain the network's topology obtained for the yeast cell cycle data.
enabled genome-wide measurements of the activity of cellular elements
and provides the analytical resources for the progress of the Systems
Biology discipline. Analysis and interpretation of gene expression data
has evolved from the gene to the pathway and interaction level, i.e.
from the detection of differentially expressed genes, to the
establishment of gene interaction networks and the identification of
enriched functional categories. Still, the understanding of biological
systems requires a further level of analysis that addresses the
characterization of the interaction between functional modules.
Results: We present a novel computational methodology to study the
functional interconnections among the molecular elements of a biological
system. The PANA approach uses high-throughput genomics measurements and
a functional annotation scheme to extract an activity profile from each
functional block -or pathway-followed by machine-learning methods to
infer the relationships between these functional profiles. The result is
a global, interconnected network of pathways that represents the
functional cross-talk within the molecular system. We have applied this
approach to describe the functional transcriptional connections during
the yeast cell cycle and to identify pathways that change their
connectivity in a disease condition using an Alzheimer example.
Conclusions: PANA is a useful tool to deepen in our understanding of the
functional interdependences that operate within complex biological
systems. We show the approach is algorithmically consistent and the
inferred network is well supported by the available functional data. The
method allows the dissection of the molecular basis of the functional
connections and we describe the different regulatory mechanisms that
explain the network's topology obtained for the yeast cell cycle data.
55.
de Diego, R. Hernandez; Boix-Chova, N.; Gomez-Cabrero, D.; Tegner, J.; Abugessaisa, I.; Conesa, A.
STATegra EMS: an Experiment Management System for complex next-generation omics experiments Journal Article
In: BMC SYSTEMS BIOLOGY, vol. 8, no. 2, 2014, ISSN: 1752-0509, (High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013).
@article{ISI:000333681300010,
title = {STATegra EMS: an Experiment Management System for complex
next-generation omics experiments},
author = { R. Hernandez de Diego and N. Boix-Chova and D. Gomez-Cabrero and J. Tegner and I. Abugessaisa and A. Conesa},
url = {http://dx.doi.org/10.1186/1752-0509-8-S2-S9},
doi = {10.1186/1752-0509-8-S2-S9},
issn = {1752-0509},
year = {2014},
date = {2014-03-01},
journal = {BMC SYSTEMS BIOLOGY},
volume = {8},
number = {2},
abstract = {High-throughput sequencing assays are now routinely used to study
different aspects of genome organization. As decreasing costs and
widespread availability of sequencing enable more laboratories to use
sequencing assays in their research projects, the number of samples and
replicates in these experiments can quickly grow to several dozens of
samples and thus require standardized annotation, storage and management
of preprocessing steps. As a part of the STATegra project, we have
developed an Experiment Management System (EMS) for high throughput
omics data that supports different types of sequencing-based assays such
as RNA-seq, ChIP-seq, Methyl-seq, etc, as well as proteomics and
metabolomics data. The STATegra EMS provides metadata annotation of
experimental design, samples and processing pipelines, as well as
storage of different types of data files, from raw data to ready-to-use
measurements. The system has been developed to provide research
laboratories with a freely-available, integrated system that offers a
simple and effective way for experiment annotation and tracking of
analysis procedures.},
note = {High-Throughput Omics and Data Integration Workshop, Barcelona, SPAIN, FEB 13-15, 2013},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
High-throughput sequencing assays are now routinely used to study
different aspects of genome organization. As decreasing costs and
widespread availability of sequencing enable more laboratories to use
sequencing assays in their research projects, the number of samples and
replicates in these experiments can quickly grow to several dozens of
samples and thus require standardized annotation, storage and management
of preprocessing steps. As a part of the STATegra project, we have
developed an Experiment Management System (EMS) for high throughput
omics data that supports different types of sequencing-based assays such
as RNA-seq, ChIP-seq, Methyl-seq, etc, as well as proteomics and
metabolomics data. The STATegra EMS provides metadata annotation of
experimental design, samples and processing pipelines, as well as
storage of different types of data files, from raw data to ready-to-use
measurements. The system has been developed to provide research
laboratories with a freely-available, integrated system that offers a
simple and effective way for experiment annotation and tracking of
analysis procedures.
different aspects of genome organization. As decreasing costs and
widespread availability of sequencing enable more laboratories to use
sequencing assays in their research projects, the number of samples and
replicates in these experiments can quickly grow to several dozens of
samples and thus require standardized annotation, storage and management
of preprocessing steps. As a part of the STATegra project, we have
developed an Experiment Management System (EMS) for high throughput
omics data that supports different types of sequencing-based assays such
as RNA-seq, ChIP-seq, Methyl-seq, etc, as well as proteomics and
metabolomics data. The STATegra EMS provides metadata annotation of
experimental design, samples and processing pipelines, as well as
storage of different types of data files, from raw data to ready-to-use
measurements. The system has been developed to provide research
laboratories with a freely-available, integrated system that offers a
simple and effective way for experiment annotation and tracking of
analysis procedures.
54.
Galan, A.; Diaz-Gimeno, P.; Poo, M. Eugenia; Valbuena, D.; Sanchez, E.; Ruiz, V.; Dopazo, J.; Montaner, D.; Conesa, A.; Simon, C.
Defining the Genomic Signature of Totipotency and Pluripotency during Early Human Development Journal Article
In: PLOS ONE, vol. 8, no. 4, 2013, ISSN: 1932-6203.
@article{ISI:000317907200122,
title = {Defining the Genomic Signature of Totipotency and Pluripotency during
Early Human Development},
author = { A. Galan and P. Diaz-Gimeno and M. Eugenia Poo and D. Valbuena and E. Sanchez and V. Ruiz and J. Dopazo and D. Montaner and A. Conesa and C. Simon},
url = {http://dx.doi.org/10.1371/journal.pone.0062135},
doi = {10.1371/journal.pone.0062135},
issn = {1932-6203},
year = {2013},
date = {2013-04-01},
journal = {PLOS ONE},
volume = {8},
number = {4},
abstract = {The genetic mechanisms governing human pre-implantation embryo
development and the in vitro counterparts, human embryonic stem cells
(hESCs), still remain incomplete. Previous global genome studies
demonstrated that totipotent blastomeres from day-3 human embryos and
pluripotent inner cell masses (ICMs) from blastocysts, display unique
and differing transcriptomes. Nevertheless, comparative gene expression
analysis has revealed that no significant differences exist between
hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental
progression. To understand early human stages evolution, we developed an
undifferentiation network signature (UNS) and applied it to a
differential gene expression profile between single blastomeres from
day-3 embryos, ICMs and hESCs. This allowed us to establish a unique
signature composed of highly interconnected genes characteristic of
totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro
pluripotency (107 genes), and which are also proprietary according to
functional analysis. This systems biology approach has led to an
improved understanding of the molecular and signaling processes
governing human pre-implantation embryo development, as well as enabling
us to comprehend how hESCs might adapt to in vitro culture conditions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The genetic mechanisms governing human pre-implantation embryo
development and the in vitro counterparts, human embryonic stem cells
(hESCs), still remain incomplete. Previous global genome studies
demonstrated that totipotent blastomeres from day-3 human embryos and
pluripotent inner cell masses (ICMs) from blastocysts, display unique
and differing transcriptomes. Nevertheless, comparative gene expression
analysis has revealed that no significant differences exist between
hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental
progression. To understand early human stages evolution, we developed an
undifferentiation network signature (UNS) and applied it to a
differential gene expression profile between single blastomeres from
day-3 embryos, ICMs and hESCs. This allowed us to establish a unique
signature composed of highly interconnected genes characteristic of
totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro
pluripotency (107 genes), and which are also proprietary according to
functional analysis. This systems biology approach has led to an
improved understanding of the molecular and signaling processes
governing human pre-implantation embryo development, as well as enabling
us to comprehend how hESCs might adapt to in vitro culture conditions.
development and the in vitro counterparts, human embryonic stem cells
(hESCs), still remain incomplete. Previous global genome studies
demonstrated that totipotent blastomeres from day-3 human embryos and
pluripotent inner cell masses (ICMs) from blastocysts, display unique
and differing transcriptomes. Nevertheless, comparative gene expression
analysis has revealed that no significant differences exist between
hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental
progression. To understand early human stages evolution, we developed an
undifferentiation network signature (UNS) and applied it to a
differential gene expression profile between single blastomeres from
day-3 embryos, ICMs and hESCs. This allowed us to establish a unique
signature composed of highly interconnected genes characteristic of
totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro
pluripotency (107 genes), and which are also proprietary according to
functional analysis. This systems biology approach has led to an
improved understanding of the molecular and signaling processes
governing human pre-implantation embryo development, as well as enabling
us to comprehend how hESCs might adapt to in vitro culture conditions.
53.
Conesa-Zamora, P.; Garcia-Solano, J.; Garcia-Garcia, F.; del Carmen Turpin, M.; Trujillo-Santos, J.; Torres-Moreno, D.; Oviedo-Ramirez, I.; Carbonell-Munoz, R.; Munoz-Delgado, E.; Rodriguez-Braun, E.; Conesa, A.; Perez-Guillermo, M.
In: INTERNATIONAL JOURNAL OF CANCER, vol. 132, no. 2, pp. 297-307, 2013, ISSN: 0020-7136.
@article{ISI:000311383600015,
title = {Expression profiling shows differential molecular pathways and provides
potential new diagnostic biomarkers for colorectal serrated
adenocarcinoma},
author = { P. Conesa-Zamora and J. Garcia-Solano and F. Garcia-Garcia and M. del Carmen Turpin and J. Trujillo-Santos and D. Torres-Moreno and I. Oviedo-Ramirez and R. Carbonell-Munoz and E. Munoz-Delgado and E. Rodriguez-Braun and A. Conesa and M. Perez-Guillermo},
url = {http://dx.doi.org/10.1002/ijc.27674},
doi = {10.1002/ijc.27674},
issn = {0020-7136},
year = {2013},
date = {2013-01-01},
journal = {INTERNATIONAL JOURNAL OF CANCER},
volume = {132},
number = {2},
pages = {297-307},
abstract = {Serrated adenocarcinoma (SAC) is a recently recognized colorectal cancer
(CRC) subtype accounting for 7.5 to 8.7% of CRCs. It has been shown
that SAC has a poorer prognosis and has different molecular and
immunohistochemical features compared with conventional carcinoma (CC)
but, to date, only one previous study has analyzed its mRNA expression
profile by microarray. Using a different microarray platform, we have
studied the molecular signature of 11 SACs and compared it with that of
15 matched CC with the aim of discerning the functions which
characterize SAC biology and validating, at the mRNA and protein level, the most differentially expressed genes which were also tested using a
validation set of 70 SACs and 70 CCs to assess their diagnostic and
prognostic values. Microarray data showed a higher representation of
morphogenesis-, hypoxia-, cytoskeleton- and vesicle transport-related
functions and also an overexpression of fascin1 (actin-bundling protein
associated with invasion) and the antiapoptotic gene hippocalcin in SAC
all of which were validated both by quantitative real-time PCR (qPCR)
and immunohistochemistry. Fascin1 expression was statistically
associated with KRAS mutation with 88.6% sensitivity and 85.7%
specificity for SAC diagnosis and the positivity of fascin1 or hippocalcin was highly suggestive of SAC diagnosis (sensitivity =
100%). Evaluation of these markers in CRCs showing histological and
molecular characteristics of high-level microsatellite instability
(MSI-H) also helped to distinguish SACs from MSI-H CRCs. Molecular
profiling demonstrates that SAC shows activation of distinct signaling
pathways and that immunohistochemical fascin1 and hippocalcin expression
can be reliably used for its differentiation from other CRC subtypes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Serrated adenocarcinoma (SAC) is a recently recognized colorectal cancer
(CRC) subtype accounting for 7.5 to 8.7% of CRCs. It has been shown
that SAC has a poorer prognosis and has different molecular and
immunohistochemical features compared with conventional carcinoma (CC)
but, to date, only one previous study has analyzed its mRNA expression
profile by microarray. Using a different microarray platform, we have
studied the molecular signature of 11 SACs and compared it with that of
15 matched CC with the aim of discerning the functions which
characterize SAC biology and validating, at the mRNA and protein level, the most differentially expressed genes which were also tested using a
validation set of 70 SACs and 70 CCs to assess their diagnostic and
prognostic values. Microarray data showed a higher representation of
morphogenesis-, hypoxia-, cytoskeleton- and vesicle transport-related
functions and also an overexpression of fascin1 (actin-bundling protein
associated with invasion) and the antiapoptotic gene hippocalcin in SAC
all of which were validated both by quantitative real-time PCR (qPCR)
and immunohistochemistry. Fascin1 expression was statistically
associated with KRAS mutation with 88.6% sensitivity and 85.7%
specificity for SAC diagnosis and the positivity of fascin1 or hippocalcin was highly suggestive of SAC diagnosis (sensitivity =
100%). Evaluation of these markers in CRCs showing histological and
molecular characteristics of high-level microsatellite instability
(MSI-H) also helped to distinguish SACs from MSI-H CRCs. Molecular
profiling demonstrates that SAC shows activation of distinct signaling
pathways and that immunohistochemical fascin1 and hippocalcin expression
can be reliably used for its differentiation from other CRC subtypes.
(CRC) subtype accounting for 7.5 to 8.7% of CRCs. It has been shown
that SAC has a poorer prognosis and has different molecular and
immunohistochemical features compared with conventional carcinoma (CC)
but, to date, only one previous study has analyzed its mRNA expression
profile by microarray. Using a different microarray platform, we have
studied the molecular signature of 11 SACs and compared it with that of
15 matched CC with the aim of discerning the functions which
characterize SAC biology and validating, at the mRNA and protein level, the most differentially expressed genes which were also tested using a
validation set of 70 SACs and 70 CCs to assess their diagnostic and
prognostic values. Microarray data showed a higher representation of
morphogenesis-, hypoxia-, cytoskeleton- and vesicle transport-related
functions and also an overexpression of fascin1 (actin-bundling protein
associated with invasion) and the antiapoptotic gene hippocalcin in SAC
all of which were validated both by quantitative real-time PCR (qPCR)
and immunohistochemistry. Fascin1 expression was statistically
associated with KRAS mutation with 88.6% sensitivity and 85.7%
specificity for SAC diagnosis and the positivity of fascin1 or hippocalcin was highly suggestive of SAC diagnosis (sensitivity =
100%). Evaluation of these markers in CRCs showing histological and
molecular characteristics of high-level microsatellite instability
(MSI-H) also helped to distinguish SACs from MSI-H CRCs. Molecular
profiling demonstrates that SAC shows activation of distinct signaling
pathways and that immunohistochemical fascin1 and hippocalcin expression
can be reliably used for its differentiation from other CRC subtypes.
52.
Yanez, Y.; Grau, E.; Canete, A.; Conesa, A.; Neira, A. Gonzalez; Castel, V.
METHYLATION STATUS IN NEUROBLASTOMA AND ITS PROGNOSTIC VALUE Journal Article
In: PEDIATRIC BLOOD & CANCER, vol. 59, no. 6, SI, pp. 1053-1054, 2012, ISSN: 1545-5009.
@article{ISI:000309754300355,
title = {METHYLATION STATUS IN NEUROBLASTOMA AND ITS PROGNOSTIC VALUE},
author = { Y. Yanez and E. Grau and A. Canete and A. Conesa and A. Gonzalez Neira and V. Castel},
issn = {1545-5009},
year = {2012},
date = {2012-12-01},
journal = {PEDIATRIC BLOOD & CANCER},
volume = {59},
number = {6, SI},
pages = {1053-1054},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
51.
Rizza, S.; Conesa, A.; Juarez, J.; Catara, A.; Navarro, L.; Duran-Vila, N.; Ancillo, G.
In: MOLECULAR PLANT PATHOLOGY, vol. 13, no. 8, pp. 852-864, 2012, ISSN: 1464-6722.
@article{ISI:000308289400005,
title = {Microarray analysis of Etrog citron (Citrus medica L.) reveals changes
in chloroplast, cell wall, peroxidase and symporter activities in
response to viroid infection},
author = { S. Rizza and A. Conesa and J. Juarez and A. Catara and L. Navarro and N. Duran-Vila and G. Ancillo},
url = {http://dx.doi.org/10.1111/j.1364-3703.2012.00794.x},
doi = {10.1111/j.1364-3703.2012.00794.x},
issn = {1464-6722},
year = {2012},
date = {2012-10-01},
journal = {MOLECULAR PLANT PATHOLOGY},
volume = {13},
number = {8},
pages = {852-864},
abstract = {Viroids are small (246401 nucleotides), single-stranded, circular RNA
molecules that infect several crop plants and can cause diseases of
economic importance. Citrus are the hosts in which the largest number of
viroids have been identified. Citrus exocortis viroid (CEVd), the causal
agent of citrus exocortis disease, induces considerable losses in citrus
crops. Changes in the gene expression profile during the early
(pre-symptomatic) and late (post-symptomatic) stages of Etrog citron
infected with CEVd were investigated using a citrus cDNA microarray.
MaSigPro analysis was performed and, on the basis of gene expression
profiles as a function of the time after infection, the differentially
expressed genes were classified into five clusters. FatiScan analysis
revealed significant enrichment of functional categories for each
cluster, indicating that viroid infection triggers important changes in
chloroplast, cell wall, peroxidase and symporter activities.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Viroids are small (246401 nucleotides), single-stranded, circular RNA
molecules that infect several crop plants and can cause diseases of
economic importance. Citrus are the hosts in which the largest number of
viroids have been identified. Citrus exocortis viroid (CEVd), the causal
agent of citrus exocortis disease, induces considerable losses in citrus
crops. Changes in the gene expression profile during the early
(pre-symptomatic) and late (post-symptomatic) stages of Etrog citron
infected with CEVd were investigated using a citrus cDNA microarray.
MaSigPro analysis was performed and, on the basis of gene expression
profiles as a function of the time after infection, the differentially
expressed genes were classified into five clusters. FatiScan analysis
revealed significant enrichment of functional categories for each
cluster, indicating that viroid infection triggers important changes in
chloroplast, cell wall, peroxidase and symporter activities.
molecules that infect several crop plants and can cause diseases of
economic importance. Citrus are the hosts in which the largest number of
viroids have been identified. Citrus exocortis viroid (CEVd), the causal
agent of citrus exocortis disease, induces considerable losses in citrus
crops. Changes in the gene expression profile during the early
(pre-symptomatic) and late (post-symptomatic) stages of Etrog citron
infected with CEVd were investigated using a citrus cDNA microarray.
MaSigPro analysis was performed and, on the basis of gene expression
profiles as a function of the time after infection, the differentially
expressed genes were classified into five clusters. FatiScan analysis
revealed significant enrichment of functional categories for each
cluster, indicating that viroid infection triggers important changes in
chloroplast, cell wall, peroxidase and symporter activities.
50.
Garcia-Alcalde, F.; Okonechnikov, K.; Carbonell, J.; Cruz, L. M.; Goetz, S.; Tarazona, S.; Dopazo, J.; Meyer, T. F.; Conesa, A.
Qualimap: evaluating next-generation sequencing alignment data Journal Article
In: BIOINFORMATICS, vol. 28, no. 20, pp. 2678-2679, 2012, ISSN: 1367-4803.
@article{ISI:000309881200016,
title = {Qualimap: evaluating next-generation sequencing alignment data},
author = { F. Garcia-Alcalde and K. Okonechnikov and J. Carbonell and L. M. Cruz and S. Goetz and S. Tarazona and J. Dopazo and T. F. Meyer and A. Conesa},
url = {http://dx.doi.org/10.1093/bioinformatics/bts503},
doi = {10.1093/bioinformatics/bts503},
issn = {1367-4803},
year = {2012},
date = {2012-10-01},
journal = {BIOINFORMATICS},
volume = {28},
number = {20},
pages = {2678-2679},
abstract = {Motivation: The sequence alignment/map (SAM) and the binary
alignment/map (BAM) formats have become the standard method of
representation of nucleotide sequence alignments for next-generation
sequencing data. SAM/BAM files usually contain information from tens to
hundreds of millions of reads. Often, the sequencing technology, protocol and/or the selected mapping algorithm introduce some unwanted
biases in these data. The systematic detection of such biases is a
non-trivial task that is crucial to drive appropriate downstream
analyses.
Results: We have developed Qualimap, a Java application that supports
user-friendly quality control of mapping data, by considering sequence
features and their genomic properties. Qualimap takes sequence alignment
data and provides graphical and statistical analyses for the evaluation
of data. Such quality-control data are vital for highlighting problems
in the sequencing and/or mapping processes, which must be addressed
prior to further analyses.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: The sequence alignment/map (SAM) and the binary
alignment/map (BAM) formats have become the standard method of
representation of nucleotide sequence alignments for next-generation
sequencing data. SAM/BAM files usually contain information from tens to
hundreds of millions of reads. Often, the sequencing technology, protocol and/or the selected mapping algorithm introduce some unwanted
biases in these data. The systematic detection of such biases is a
non-trivial task that is crucial to drive appropriate downstream
analyses.
Results: We have developed Qualimap, a Java application that supports
user-friendly quality control of mapping data, by considering sequence
features and their genomic properties. Qualimap takes sequence alignment
data and provides graphical and statistical analyses for the evaluation
of data. Such quality-control data are vital for highlighting problems
in the sequencing and/or mapping processes, which must be addressed
prior to further analyses.
alignment/map (BAM) formats have become the standard method of
representation of nucleotide sequence alignments for next-generation
sequencing data. SAM/BAM files usually contain information from tens to
hundreds of millions of reads. Often, the sequencing technology, protocol and/or the selected mapping algorithm introduce some unwanted
biases in these data. The systematic detection of such biases is a
non-trivial task that is crucial to drive appropriate downstream
analyses.
Results: We have developed Qualimap, a Java application that supports
user-friendly quality control of mapping data, by considering sequence
features and their genomic properties. Qualimap takes sequence alignment
data and provides graphical and statistical analyses for the evaluation
of data. Such quality-control data are vital for highlighting problems
in the sequencing and/or mapping processes, which must be addressed
prior to further analyses.
49.
Fernandez, P.; Soria, M.; Blesa, D.; DiRienzo, J.; Moschen, S.; Rivarola, M.; Clavijo, B. Jose; Gonzalez, S.; Peluffo, L.; Principi, D.; Dosio, G.; Aguirrezabal, L.; Garcia-Garcia, F.; Conesa, A.; Hopp, E.; Dopazo, J.; Heinz, R. Amelia; Paniego, N.
In: PLOS ONE, vol. 7, no. 10, 2012, ISSN: 1932-6203.
@article{ISI:000310262500003,
title = {Development, Characterization and Experimental Validation of a
Cultivated Sunflower (Helianthus annuus L.) Gene Expression
Oligonucleotide Microarray},
author = { P. Fernandez and M. Soria and D. Blesa and J. DiRienzo and S. Moschen and M. Rivarola and B. Jose Clavijo and S. Gonzalez and L. Peluffo and D. Principi and G. Dosio and L. Aguirrezabal and F. Garcia-Garcia and A. Conesa and E. Hopp and J. Dopazo and R. Amelia Heinz and N. Paniego},
url = {http://dx.doi.org/10.1371/journal.pone.0045899},
doi = {10.1371/journal.pone.0045899},
issn = {1932-6203},
year = {2012},
date = {2012-10-01},
journal = {PLOS ONE},
volume = {7},
number = {10},
abstract = {Oligonucleotide-based microarrays with accurate gene coverage represent
a key strategy for transcriptional studies in orphan species such as
sunflower, H. annuus L., which lacks full genome sequences. The goal of
this study was the development and functional annotation of a
comprehensive sunflower unigene collection and the design and validation
of a custom sunflower oligonucleotide-based microarray. A large scale
EST (>130,000 ESTs) curation, assembly and sequence annotation was
performed using Blast2GO (www.blast2go.de). The EST assembly comprises
41,013 putative transcripts (12,924 contigs and 28,089 singletons). The
resulting Sunflower Unigen Resource (SUR version 1.0) was used to design
an oligonucleotide-based Agilent microarray for cultivated sunflower.
This microarray includes a total of 42,326 features: 1,417 Agilent
controls, 74 control probes for sunflower replicated 10 times (740
controls) and 40,169 different non-control probes. Microarray
performance was validated using a model experiment examining the
induction of senescence by water deficit. Pre-processing and
differential expression analysis of Agilent microarrays was performed
using the Bioconductor limma package. The analyses based on p-values
calculated by eBayes (p<0.01) allowed the detection of 558
differentially expressed genes between water stress and control
conditions; from these, ten genes were further validated by qPCR.
Over-represented ontologies were identified using FatiScan in the
Babelomics suite. This work generated a curated and trustable sunflower
unigene collection, and a custom, validated sunflower
oligonucleotide-based microarray using Agilent technology. Both the
curated unigene collection and the validated oligonucleotide microarray
provide key resources for sunflower genome analysis, transcriptional
studies, and molecular breeding for crop improvement.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Oligonucleotide-based microarrays with accurate gene coverage represent
a key strategy for transcriptional studies in orphan species such as
sunflower, H. annuus L., which lacks full genome sequences. The goal of
this study was the development and functional annotation of a
comprehensive sunflower unigene collection and the design and validation
of a custom sunflower oligonucleotide-based microarray. A large scale
EST (>130,000 ESTs) curation, assembly and sequence annotation was
performed using Blast2GO (www.blast2go.de). The EST assembly comprises
41,013 putative transcripts (12,924 contigs and 28,089 singletons). The
resulting Sunflower Unigen Resource (SUR version 1.0) was used to design
an oligonucleotide-based Agilent microarray for cultivated sunflower.
This microarray includes a total of 42,326 features: 1,417 Agilent
controls, 74 control probes for sunflower replicated 10 times (740
controls) and 40,169 different non-control probes. Microarray
performance was validated using a model experiment examining the
induction of senescence by water deficit. Pre-processing and
differential expression analysis of Agilent microarrays was performed
using the Bioconductor limma package. The analyses based on p-values
calculated by eBayes (p<0.01) allowed the detection of 558
differentially expressed genes between water stress and control
conditions; from these, ten genes were further validated by qPCR.
Over-represented ontologies were identified using FatiScan in the
Babelomics suite. This work generated a curated and trustable sunflower
unigene collection, and a custom, validated sunflower
oligonucleotide-based microarray using Agilent technology. Both the
curated unigene collection and the validated oligonucleotide microarray
provide key resources for sunflower genome analysis, transcriptional
studies, and molecular breeding for crop improvement.
a key strategy for transcriptional studies in orphan species such as
sunflower, H. annuus L., which lacks full genome sequences. The goal of
this study was the development and functional annotation of a
comprehensive sunflower unigene collection and the design and validation
of a custom sunflower oligonucleotide-based microarray. A large scale
EST (>130,000 ESTs) curation, assembly and sequence annotation was
performed using Blast2GO (www.blast2go.de). The EST assembly comprises
41,013 putative transcripts (12,924 contigs and 28,089 singletons). The
resulting Sunflower Unigen Resource (SUR version 1.0) was used to design
an oligonucleotide-based Agilent microarray for cultivated sunflower.
This microarray includes a total of 42,326 features: 1,417 Agilent
controls, 74 control probes for sunflower replicated 10 times (740
controls) and 40,169 different non-control probes. Microarray
performance was validated using a model experiment examining the
induction of senescence by water deficit. Pre-processing and
differential expression analysis of Agilent microarrays was performed
using the Bioconductor limma package. The analyses based on p-values
calculated by eBayes (p<0.01) allowed the detection of 558
differentially expressed genes between water stress and control
conditions; from these, ten genes were further validated by qPCR.
Over-represented ontologies were identified using FatiScan in the
Babelomics suite. This work generated a curated and trustable sunflower
unigene collection, and a custom, validated sunflower
oligonucleotide-based microarray using Agilent technology. Both the
curated unigene collection and the validated oligonucleotide microarray
provide key resources for sunflower genome analysis, transcriptional
studies, and molecular breeding for crop improvement.
48.
Agusti, J.; Gimeno, J.; Merelo, P.; Serrano, R.; Cercos, M.; Conesa, A.; Talon, M.; Tadeo, F. R.
In: JOURNAL OF EXPERIMENTAL BOTANY, vol. 63, no. 17, pp. 6079-6091, 2012, ISSN: 0022-0957.
@article{ISI:000310368300003,
title = {Early gene expression events in the laminar abscission zone of
abscission-promoted citrus leaves after a cycle of water
stress/rehydration: involvement of CitbHLH1},
author = { J. Agusti and J. Gimeno and P. Merelo and R. Serrano and M. Cercos and A. Conesa and M. Talon and F. R. Tadeo},
url = {http://dx.doi.org/10.1093/jxb/ers270},
doi = {10.1093/jxb/ers270},
issn = {0022-0957},
year = {2012},
date = {2012-10-01},
journal = {JOURNAL OF EXPERIMENTAL BOTANY},
volume = {63},
number = {17},
pages = {6079-6091},
abstract = {Leaf abscission is a common response of plants to drought stress. Some
species, such as citrus, have evolved a specific behaviour in this
respect, keeping their leaves attached to the plant body during water
stress until this is released by irrigation or rain. This study
successfully reproduced this phenomenon under controlled conditions (24h
of water stress followed by 24h of rehydration) and used it to construct
a suppression subtractive hybridization cDNA library enriched in genes
involved in the early stages of rehydration-promoted leaf abscission
after water stress. Sequencing of the library yielded 314 unigenes, which were spotted onto nylon membranes. Membrane hybridization with
petiole (Pet)- and laminar abscission zone (LAZ)-enriched RNA samples
corresponding to early steps in leaf abscission revealed an almost
exclusive preferential gene expression programme in the LAZ. The data
identified major processes such as protein metabolism, cell-wall
modification, signalling, control of transcription and vesicle
production, and transport as the main biological processes activated in
LAZs during the early steps of rehydration-promoted leaf abscission
after water stress. Based on these findings, a model for the early steps
of citrus leaf abscission is proposed. In addition, it is suggested that
CitbHLH1, the putative citrus orthologue of Arabidopsis BIGPETAL, may
play major roles in the control of abscission-related events in citrus
abscission zones.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Leaf abscission is a common response of plants to drought stress. Some
species, such as citrus, have evolved a specific behaviour in this
respect, keeping their leaves attached to the plant body during water
stress until this is released by irrigation or rain. This study
successfully reproduced this phenomenon under controlled conditions (24h
of water stress followed by 24h of rehydration) and used it to construct
a suppression subtractive hybridization cDNA library enriched in genes
involved in the early stages of rehydration-promoted leaf abscission
after water stress. Sequencing of the library yielded 314 unigenes, which were spotted onto nylon membranes. Membrane hybridization with
petiole (Pet)- and laminar abscission zone (LAZ)-enriched RNA samples
corresponding to early steps in leaf abscission revealed an almost
exclusive preferential gene expression programme in the LAZ. The data
identified major processes such as protein metabolism, cell-wall
modification, signalling, control of transcription and vesicle
production, and transport as the main biological processes activated in
LAZs during the early steps of rehydration-promoted leaf abscission
after water stress. Based on these findings, a model for the early steps
of citrus leaf abscission is proposed. In addition, it is suggested that
CitbHLH1, the putative citrus orthologue of Arabidopsis BIGPETAL, may
play major roles in the control of abscission-related events in citrus
abscission zones.
species, such as citrus, have evolved a specific behaviour in this
respect, keeping their leaves attached to the plant body during water
stress until this is released by irrigation or rain. This study
successfully reproduced this phenomenon under controlled conditions (24h
of water stress followed by 24h of rehydration) and used it to construct
a suppression subtractive hybridization cDNA library enriched in genes
involved in the early stages of rehydration-promoted leaf abscission
after water stress. Sequencing of the library yielded 314 unigenes, which were spotted onto nylon membranes. Membrane hybridization with
petiole (Pet)- and laminar abscission zone (LAZ)-enriched RNA samples
corresponding to early steps in leaf abscission revealed an almost
exclusive preferential gene expression programme in the LAZ. The data
identified major processes such as protein metabolism, cell-wall
modification, signalling, control of transcription and vesicle
production, and transport as the main biological processes activated in
LAZs during the early steps of rehydration-promoted leaf abscission
after water stress. Based on these findings, a model for the early steps
of citrus leaf abscission is proposed. In addition, it is suggested that
CitbHLH1, the putative citrus orthologue of Arabidopsis BIGPETAL, may
play major roles in the control of abscission-related events in citrus
abscission zones.
47.
Nueda, M. J.; Ferrer, A.; Conesa, A.
ARSyN: a method for the identification and removal of systematic noise in multifactorial time course microarray experiments Journal Article
In: BIOSTATISTICS, vol. 13, no. 3, pp. 553-566, 2012, ISSN: 1465-4644.
@article{ISI:000305420000014,
title = {ARSyN: a method for the identification and removal of systematic noise
in multifactorial time course microarray experiments},
author = { M. J. Nueda and A. Ferrer and A. Conesa},
url = {http://dx.doi.org/10.1093/biostatistics/kxr042},
doi = {10.1093/biostatistics/kxr042},
issn = {1465-4644},
year = {2012},
date = {2012-07-01},
journal = {BIOSTATISTICS},
volume = {13},
number = {3},
pages = {553-566},
abstract = {Transcriptomic profiling experiments that aim to the identification of
responsive genes in specific biological conditions are commonly set up
under defined experimental designs that try to assess the effects of
factors and their interactions on gene expression. Data from these
controlled experiments, however, may also contain sources of unwanted
noise that can distort the signal under study, affect the residuals of
applied statistical models, and hamper data analysis. Commonly, normalization methods are applied to transcriptomics data to remove
technical artifacts, but these are normally based on general assumptions
of transcript distribution and greatly ignore both the characteristics
of the experiment under consideration and the coordinative nature of
gene expression. In this paper, we propose a novel methodology, ARSyN, for the preprocessing of microarray data that takes into account these 2
last aspects. By combining analysis of variance (ANOVA) modeling of gene
expression values and multivariate analysis of estimated effects, the
method identifies the nonstructured part of the signal associated to the
experimental factors (the noise within the signal) and the structured
variation of the ANOVA errors (the signal of the noise). By removing
these noise fractions from the original data, we create a filtered data
set that is rich in the information of interest and includes only the
random noise required for inferential analysis. In this work, we focus
on multifactorial time course microarray (MTCM) experiments with 2
factors: one quantitative such as time or dosage and the other
qualitative, as tissue, strain, or treatment. However, the method can be
used in other situations such as experiments with only one factor or
more complex designs with more than 2 factors. The filtered data
obtained after applying ARSyN can be further analyzed with the
appropriate statistical technique to obtain the biological information
required. To evaluate the performance of the filtering strategy, we have
applied different statistical approaches for MTCM analysis to several
real and simulated data sets, studying also the efficiency of these
techniques. By comparing the results obtained with the original and
ARSyN filtered data and also with other filtering techniques, we can
conclude that the proposed method increases the statistical power to
detect biological signals, especially in cases where there are high
levels of structural noise. Software for ARSyN is freely available at
http://www.ua.es/personal/mj.nueda.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Transcriptomic profiling experiments that aim to the identification of
responsive genes in specific biological conditions are commonly set up
under defined experimental designs that try to assess the effects of
factors and their interactions on gene expression. Data from these
controlled experiments, however, may also contain sources of unwanted
noise that can distort the signal under study, affect the residuals of
applied statistical models, and hamper data analysis. Commonly, normalization methods are applied to transcriptomics data to remove
technical artifacts, but these are normally based on general assumptions
of transcript distribution and greatly ignore both the characteristics
of the experiment under consideration and the coordinative nature of
gene expression. In this paper, we propose a novel methodology, ARSyN, for the preprocessing of microarray data that takes into account these 2
last aspects. By combining analysis of variance (ANOVA) modeling of gene
expression values and multivariate analysis of estimated effects, the
method identifies the nonstructured part of the signal associated to the
experimental factors (the noise within the signal) and the structured
variation of the ANOVA errors (the signal of the noise). By removing
these noise fractions from the original data, we create a filtered data
set that is rich in the information of interest and includes only the
random noise required for inferential analysis. In this work, we focus
on multifactorial time course microarray (MTCM) experiments with 2
factors: one quantitative such as time or dosage and the other
qualitative, as tissue, strain, or treatment. However, the method can be
used in other situations such as experiments with only one factor or
more complex designs with more than 2 factors. The filtered data
obtained after applying ARSyN can be further analyzed with the
appropriate statistical technique to obtain the biological information
required. To evaluate the performance of the filtering strategy, we have
applied different statistical approaches for MTCM analysis to several
real and simulated data sets, studying also the efficiency of these
techniques. By comparing the results obtained with the original and
ARSyN filtered data and also with other filtering techniques, we can
conclude that the proposed method increases the statistical power to
detect biological signals, especially in cases where there are high
levels of structural noise. Software for ARSyN is freely available at
http://www.ua.es/personal/mj.nueda.
responsive genes in specific biological conditions are commonly set up
under defined experimental designs that try to assess the effects of
factors and their interactions on gene expression. Data from these
controlled experiments, however, may also contain sources of unwanted
noise that can distort the signal under study, affect the residuals of
applied statistical models, and hamper data analysis. Commonly, normalization methods are applied to transcriptomics data to remove
technical artifacts, but these are normally based on general assumptions
of transcript distribution and greatly ignore both the characteristics
of the experiment under consideration and the coordinative nature of
gene expression. In this paper, we propose a novel methodology, ARSyN, for the preprocessing of microarray data that takes into account these 2
last aspects. By combining analysis of variance (ANOVA) modeling of gene
expression values and multivariate analysis of estimated effects, the
method identifies the nonstructured part of the signal associated to the
experimental factors (the noise within the signal) and the structured
variation of the ANOVA errors (the signal of the noise). By removing
these noise fractions from the original data, we create a filtered data
set that is rich in the information of interest and includes only the
random noise required for inferential analysis. In this work, we focus
on multifactorial time course microarray (MTCM) experiments with 2
factors: one quantitative such as time or dosage and the other
qualitative, as tissue, strain, or treatment. However, the method can be
used in other situations such as experiments with only one factor or
more complex designs with more than 2 factors. The filtered data
obtained after applying ARSyN can be further analyzed with the
appropriate statistical technique to obtain the biological information
required. To evaluate the performance of the filtering strategy, we have
applied different statistical approaches for MTCM analysis to several
real and simulated data sets, studying also the efficiency of these
techniques. By comparing the results obtained with the original and
ARSyN filtered data and also with other filtering techniques, we can
conclude that the proposed method increases the statistical power to
detect biological signals, especially in cases where there are high
levels of structural noise. Software for ARSyN is freely available at
http://www.ua.es/personal/mj.nueda.
46.
Lin, C. J.; Irmer, H.; Tarazona, S.; Olbermann, P.; Krappmann, S.; Conesa, A.; Braus, G.
Regulatory proteins in the opportunistic human pathogen Aspergillus fumigatus Journal Article
In: MYCOSES, vol. 55, no. 4, SI, pp. 135-136, 2012, ISSN: 0933-7407.
@article{ISI:000305069800421,
title = {Regulatory proteins in the opportunistic human pathogen Aspergillus
fumigatus},
author = { C. J. Lin and H. Irmer and S. Tarazona and P. Olbermann and S. Krappmann and A. Conesa and G. Braus},
issn = {0933-7407},
year = {2012},
date = {2012-06-01},
journal = {MYCOSES},
volume = {55},
number = {4, SI},
pages = {135-136},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
45.
Jaime, M. D. L. A.; Lopez-Llorca, L. Vicente; Conesa, A.; Lee, A. Y.; Proctor, M.; Heisler, L. E.; Gebbia, M.; Giaever, G.; Westwood, J. T.; Nislow, C.
Identification of yeast genes that confer resistance to chitosan oligosaccharide (COS) using chemogenomics Journal Article
In: BMC GENOMICS, vol. 13, 2012, ISSN: 1471-2164.
@article{ISI:000311518100001,
title = {Identification of yeast genes that confer resistance to chitosan
oligosaccharide (COS) using chemogenomics},
author = { M. D. L. A. Jaime and L. Vicente Lopez-Llorca and A. Conesa and A. Y. Lee and M. Proctor and L. E. Heisler and M. Gebbia and G. Giaever and J. T. Westwood and C. Nislow},
url = {http://dx.doi.org/10.1186/1471-2164-13-267},
doi = {10.1186/1471-2164-13-267},
issn = {1471-2164},
year = {2012},
date = {2012-06-01},
journal = {BMC GENOMICS},
volume = {13},
abstract = {Background: Chitosan oligosaccharide (COS), a deacetylated derivative of
chitin, is an abundant, and renewable natural polymer. COS has higher
antimicrobial properties than chitosan and is presumed to act by
disrupting/permeabilizing the cell membranes of bacteria, yeast and
fungi. COS is relatively non-toxic to mammals. By identifying the
molecular and genetic targets of COS, we hope to gain a better
understanding of the antifungal mode of action of COS.
Results: Three different chemogenomic fitness assays, haploinsufficiency
(HIP), homozygous deletion (HOP), and multicopy suppression (MSP)
profiling were combined with a transcriptomic analysis to gain insight
in to the mode of action and mechanisms of resistance to chitosan
oligosaccharides. The fitness assays identified 39 yeast deletion
strains sensitive to COS and 21 suppressors of COS sensitivity. The
genes identified are involved in processes such as RNA biology
(transcription, translation and regulatory mechanisms), membrane
functions (e.g. signalling, transport and targeting), membrane
structural components, cell division, and proteasome processes. The
transcriptomes of control wild type and 5 suppressor strains
overexpressing ARL1, BCK2, ERG24, MSG5, or RBA50, were analyzed in the
presence and absence of COS. Some of the up-regulated transcripts in the
suppressor overexpressing strains exposed to COS included genes involved
in transcription, cell cycle, stress response and the Ras signal
transduction pathway. Down-regulated transcripts included those encoding
protein folding components and respiratory chain proteins. The
COS-induced transcriptional response is distinct from previously
described environmental stress responses (i.e. thermal, salt, osmotic
and oxidative stress) and pre-treatment with these well characterized
environmental stressors provided little or any resistance to COS.
Conclusions: Overexpression of the ARL1 gene, a member of the Ras
superfamily that regulates membrane trafficking, provides protection
against COS-induced cell membrane permeability and damage. We found that
the ARL1 COS-resistant over-expression strain was as sensitive to
Amphotericin B, Fluconazole and Terbinafine as the wild type cells and
that when COS and Fluconazole are used in combination they act in a
synergistic fashion. The gene targets of COS identified in this study
indicate that COS's mechanism of action is different from other commonly
studied fungicides that target membranes, suggesting that COS may be an
effective fungicide for drug-resistant fungal pathogens.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Chitosan oligosaccharide (COS), a deacetylated derivative of
chitin, is an abundant, and renewable natural polymer. COS has higher
antimicrobial properties than chitosan and is presumed to act by
disrupting/permeabilizing the cell membranes of bacteria, yeast and
fungi. COS is relatively non-toxic to mammals. By identifying the
molecular and genetic targets of COS, we hope to gain a better
understanding of the antifungal mode of action of COS.
Results: Three different chemogenomic fitness assays, haploinsufficiency
(HIP), homozygous deletion (HOP), and multicopy suppression (MSP)
profiling were combined with a transcriptomic analysis to gain insight
in to the mode of action and mechanisms of resistance to chitosan
oligosaccharides. The fitness assays identified 39 yeast deletion
strains sensitive to COS and 21 suppressors of COS sensitivity. The
genes identified are involved in processes such as RNA biology
(transcription, translation and regulatory mechanisms), membrane
functions (e.g. signalling, transport and targeting), membrane
structural components, cell division, and proteasome processes. The
transcriptomes of control wild type and 5 suppressor strains
overexpressing ARL1, BCK2, ERG24, MSG5, or RBA50, were analyzed in the
presence and absence of COS. Some of the up-regulated transcripts in the
suppressor overexpressing strains exposed to COS included genes involved
in transcription, cell cycle, stress response and the Ras signal
transduction pathway. Down-regulated transcripts included those encoding
protein folding components and respiratory chain proteins. The
COS-induced transcriptional response is distinct from previously
described environmental stress responses (i.e. thermal, salt, osmotic
and oxidative stress) and pre-treatment with these well characterized
environmental stressors provided little or any resistance to COS.
Conclusions: Overexpression of the ARL1 gene, a member of the Ras
superfamily that regulates membrane trafficking, provides protection
against COS-induced cell membrane permeability and damage. We found that
the ARL1 COS-resistant over-expression strain was as sensitive to
Amphotericin B, Fluconazole and Terbinafine as the wild type cells and
that when COS and Fluconazole are used in combination they act in a
synergistic fashion. The gene targets of COS identified in this study
indicate that COS's mechanism of action is different from other commonly
studied fungicides that target membranes, suggesting that COS may be an
effective fungicide for drug-resistant fungal pathogens.
chitin, is an abundant, and renewable natural polymer. COS has higher
antimicrobial properties than chitosan and is presumed to act by
disrupting/permeabilizing the cell membranes of bacteria, yeast and
fungi. COS is relatively non-toxic to mammals. By identifying the
molecular and genetic targets of COS, we hope to gain a better
understanding of the antifungal mode of action of COS.
Results: Three different chemogenomic fitness assays, haploinsufficiency
(HIP), homozygous deletion (HOP), and multicopy suppression (MSP)
profiling were combined with a transcriptomic analysis to gain insight
in to the mode of action and mechanisms of resistance to chitosan
oligosaccharides. The fitness assays identified 39 yeast deletion
strains sensitive to COS and 21 suppressors of COS sensitivity. The
genes identified are involved in processes such as RNA biology
(transcription, translation and regulatory mechanisms), membrane
functions (e.g. signalling, transport and targeting), membrane
structural components, cell division, and proteasome processes. The
transcriptomes of control wild type and 5 suppressor strains
overexpressing ARL1, BCK2, ERG24, MSG5, or RBA50, were analyzed in the
presence and absence of COS. Some of the up-regulated transcripts in the
suppressor overexpressing strains exposed to COS included genes involved
in transcription, cell cycle, stress response and the Ras signal
transduction pathway. Down-regulated transcripts included those encoding
protein folding components and respiratory chain proteins. The
COS-induced transcriptional response is distinct from previously
described environmental stress responses (i.e. thermal, salt, osmotic
and oxidative stress) and pre-treatment with these well characterized
environmental stressors provided little or any resistance to COS.
Conclusions: Overexpression of the ARL1 gene, a member of the Ras
superfamily that regulates membrane trafficking, provides protection
against COS-induced cell membrane permeability and damage. We found that
the ARL1 COS-resistant over-expression strain was as sensitive to
Amphotericin B, Fluconazole and Terbinafine as the wild type cells and
that when COS and Fluconazole are used in combination they act in a
synergistic fashion. The gene targets of COS identified in this study
indicate that COS's mechanism of action is different from other commonly
studied fungicides that target membranes, suggesting that COS may be an
effective fungicide for drug-resistant fungal pathogens.
44.
Perez-Quintero, A. L.; Sablok, G.; Tatarinova, T. V.; Conesa, A.; Kuo, J.; Lopez, C.
Mining of miRNAs and potential targets from gene oriented clusters of transcripts sequences of the anti-malarial plant, Artemisia annua Journal Article
In: BIOTECHNOLOGY LETTERS, vol. 34, no. 4, pp. 737-745, 2012, ISSN: 0141-5492.
@article{ISI:000301295900020,
title = {Mining of miRNAs and potential targets from gene oriented clusters of
transcripts sequences of the anti-malarial plant, Artemisia annua},
author = { A. L. Perez-Quintero and G. Sablok and T. V. Tatarinova and A. Conesa and J. Kuo and C. Lopez},
url = {http://dx.doi.org/10.1007/s10529-011-0808-0},
doi = {10.1007/s10529-011-0808-0},
issn = {0141-5492},
year = {2012},
date = {2012-04-01},
journal = {BIOTECHNOLOGY LETTERS},
volume = {34},
number = {4},
pages = {737-745},
abstract = {miRNAs involved in the biosynthesis of artemisinin, an anti-malarial
compound form the plant Artemisia annua, have been identified using
computational approaches to find conserved pre-miRNAs in available A.
annua UniGene collections. Eleven pre-miRNAs were found from nine
families. Targets predicted for these miRNAs were mainly transcription
factors for conserved miRNAs. No target genes involved in artemisinin
biosynthesis were found. However, miR390 was predicted to target a gene
involved in the trichome development, which is the site of synthesis of
artemisinin and could be a candidate for genetic transformation aiming
to increase the content of artemisinin. Phylogenetic analyses were
carried out to determinate the relation between A. annua and other plant
pre-miRNAs: the pre-miRNA-based phylogenetic trees failed to correspond
to known phylogenies, suggesting that pre-miRNA primary sequences may be
too variable to accurately predict phylogenetic relations.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
miRNAs involved in the biosynthesis of artemisinin, an anti-malarial
compound form the plant Artemisia annua, have been identified using
computational approaches to find conserved pre-miRNAs in available A.
annua UniGene collections. Eleven pre-miRNAs were found from nine
families. Targets predicted for these miRNAs were mainly transcription
factors for conserved miRNAs. No target genes involved in artemisinin
biosynthesis were found. However, miR390 was predicted to target a gene
involved in the trichome development, which is the site of synthesis of
artemisinin and could be a candidate for genetic transformation aiming
to increase the content of artemisinin. Phylogenetic analyses were
carried out to determinate the relation between A. annua and other plant
pre-miRNAs: the pre-miRNA-based phylogenetic trees failed to correspond
to known phylogenies, suggesting that pre-miRNA primary sequences may be
too variable to accurately predict phylogenetic relations.
compound form the plant Artemisia annua, have been identified using
computational approaches to find conserved pre-miRNAs in available A.
annua UniGene collections. Eleven pre-miRNAs were found from nine
families. Targets predicted for these miRNAs were mainly transcription
factors for conserved miRNAs. No target genes involved in artemisinin
biosynthesis were found. However, miR390 was predicted to target a gene
involved in the trichome development, which is the site of synthesis of
artemisinin and could be a candidate for genetic transformation aiming
to increase the content of artemisinin. Phylogenetic analyses were
carried out to determinate the relation between A. annua and other plant
pre-miRNAs: the pre-miRNA-based phylogenetic trees failed to correspond
to known phylogenies, suggesting that pre-miRNA primary sequences may be
too variable to accurately predict phylogenetic relations.
43.
Oppert, B.; Dowd, S. E.; Bouffard, P.; Li, L.; Conesa, A.; Lorenzen, M. D.; Toutges, M.; Marshall, J.; Huestis, D. L.; Fabrick, J.; Oppert, C.; Jurat-Fuentes, J. L.
Transcriptome Profiling of the Intoxication Response of Tenebrio molitor Larvae to Bacillus thuringiensis Cry3Aa Protoxin Journal Article
In: PLOS ONE, vol. 7, no. 4, 2012, ISSN: 1932-6203.
@article{ISI:000305345200011,
title = {Transcriptome Profiling of the Intoxication Response of Tenebrio molitor
Larvae to Bacillus thuringiensis Cry3Aa Protoxin},
author = { B. Oppert and S. E. Dowd and P. Bouffard and L. Li and A. Conesa and M. D. Lorenzen and M. Toutges and J. Marshall and D. L. Huestis and J. Fabrick and C. Oppert and J. L. Jurat-Fuentes},
url = {http://dx.doi.org/10.1371/journal.pone.0034624},
doi = {10.1371/journal.pone.0034624},
issn = {1932-6203},
year = {2012},
date = {2012-04-01},
journal = {PLOS ONE},
volume = {7},
number = {4},
abstract = {Bacillus thuringiensis (Bt) crystal (Cry) proteins are effective against
a select number of insect pests, but improvements are needed to increase
efficacy and decrease time to mortality for coleopteran pests. To gain
insight into the Bt intoxication process in Coleoptera, we performed
RNA-Seq on cDNA generated from the guts of Tenebrio molitor larvae that
consumed either a control diet or a diet containing Cry3Aa protoxin.
Approximately 134,090 and 124,287 sequence reads from the control and
Cry3Aa-treated groups were assembled into 1,318 and 1,140 contigs, respectively. Enrichment analyses indicated that functions associated
with mitochondrial respiration, signalling, maintenance of cell
structure, membrane integrity, protein recycling/synthesis, and glycosyl
hydrolases were significantly increased in Cry3Aa-treated larvae, whereas functions associated with many metabolic processes were reduced, especially glycolysis, tricarboxylic acid cycle, and fatty acid
synthesis. Microarray analysis was used to evaluate temporal changes in
gene expression after 6, 12 or 24 h of Cry3Aa exposure. Overall, microarray analysis indicated that transcripts related to allergens, chitin-binding proteins, glycosyl hydrolases, and tubulins were induced, and those related to immunity and metabolism were repressed in
Cry3Aa-intoxicated larvae. The 24 h microarray data validated most of
the RNA-Seq data. Of the three intoxication intervals, larvae
demonstrated more differential expression of transcripts after 12 h
exposure to Cry3Aa. Gene expression examined by three different methods
in control vs. Cry3Aa-treated larvae at the 24 h time point indicated
that transcripts encoding proteins with chitin-binding domain 3 were the
most differentially expressed in Cry3Aa-intoxicated larvae. Overall, the
data suggest that T. molitor larvae mount a complex response to Cry3Aa
during the initial 24 h of intoxication. Data from this study represent
the largest genetic sequence dataset for T. molitor to date.
Furthermore, the methods in this study are useful for comparative
analyses in organisms lacking a sequenced genome.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bacillus thuringiensis (Bt) crystal (Cry) proteins are effective against
a select number of insect pests, but improvements are needed to increase
efficacy and decrease time to mortality for coleopteran pests. To gain
insight into the Bt intoxication process in Coleoptera, we performed
RNA-Seq on cDNA generated from the guts of Tenebrio molitor larvae that
consumed either a control diet or a diet containing Cry3Aa protoxin.
Approximately 134,090 and 124,287 sequence reads from the control and
Cry3Aa-treated groups were assembled into 1,318 and 1,140 contigs, respectively. Enrichment analyses indicated that functions associated
with mitochondrial respiration, signalling, maintenance of cell
structure, membrane integrity, protein recycling/synthesis, and glycosyl
hydrolases were significantly increased in Cry3Aa-treated larvae, whereas functions associated with many metabolic processes were reduced, especially glycolysis, tricarboxylic acid cycle, and fatty acid
synthesis. Microarray analysis was used to evaluate temporal changes in
gene expression after 6, 12 or 24 h of Cry3Aa exposure. Overall, microarray analysis indicated that transcripts related to allergens, chitin-binding proteins, glycosyl hydrolases, and tubulins were induced, and those related to immunity and metabolism were repressed in
Cry3Aa-intoxicated larvae. The 24 h microarray data validated most of
the RNA-Seq data. Of the three intoxication intervals, larvae
demonstrated more differential expression of transcripts after 12 h
exposure to Cry3Aa. Gene expression examined by three different methods
in control vs. Cry3Aa-treated larvae at the 24 h time point indicated
that transcripts encoding proteins with chitin-binding domain 3 were the
most differentially expressed in Cry3Aa-intoxicated larvae. Overall, the
data suggest that T. molitor larvae mount a complex response to Cry3Aa
during the initial 24 h of intoxication. Data from this study represent
the largest genetic sequence dataset for T. molitor to date.
Furthermore, the methods in this study are useful for comparative
analyses in organisms lacking a sequenced genome.
a select number of insect pests, but improvements are needed to increase
efficacy and decrease time to mortality for coleopteran pests. To gain
insight into the Bt intoxication process in Coleoptera, we performed
RNA-Seq on cDNA generated from the guts of Tenebrio molitor larvae that
consumed either a control diet or a diet containing Cry3Aa protoxin.
Approximately 134,090 and 124,287 sequence reads from the control and
Cry3Aa-treated groups were assembled into 1,318 and 1,140 contigs, respectively. Enrichment analyses indicated that functions associated
with mitochondrial respiration, signalling, maintenance of cell
structure, membrane integrity, protein recycling/synthesis, and glycosyl
hydrolases were significantly increased in Cry3Aa-treated larvae, whereas functions associated with many metabolic processes were reduced, especially glycolysis, tricarboxylic acid cycle, and fatty acid
synthesis. Microarray analysis was used to evaluate temporal changes in
gene expression after 6, 12 or 24 h of Cry3Aa exposure. Overall, microarray analysis indicated that transcripts related to allergens, chitin-binding proteins, glycosyl hydrolases, and tubulins were induced, and those related to immunity and metabolism were repressed in
Cry3Aa-intoxicated larvae. The 24 h microarray data validated most of
the RNA-Seq data. Of the three intoxication intervals, larvae
demonstrated more differential expression of transcripts after 12 h
exposure to Cry3Aa. Gene expression examined by three different methods
in control vs. Cry3Aa-treated larvae at the 24 h time point indicated
that transcripts encoding proteins with chitin-binding domain 3 were the
most differentially expressed in Cry3Aa-intoxicated larvae. Overall, the
data suggest that T. molitor larvae mount a complex response to Cry3Aa
during the initial 24 h of intoxication. Data from this study represent
the largest genetic sequence dataset for T. molitor to date.
Furthermore, the methods in this study are useful for comparative
analyses in organisms lacking a sequenced genome.
42.
Carcel-Trullols, J.; Aguilar-Gallardo, C.; Garcia-Alcalde, F.; Pardo-Cea, M. Angel; Dopazo, J.; Conesa, A.; Simon, C.
Transdifferentiation of MALME-3M and MCF-7 Cells toward Adipocyte-like Cells is Dependent on Clathrin-mediated Endocytosis Journal Article
In: SPRINGERPLUS, vol. 1, 2012, ISSN: 2193-1801.
@article{ISI:000209459000044,
title = {Transdifferentiation of MALME-3M and MCF-7 Cells toward Adipocyte-like
Cells is Dependent on Clathrin-mediated Endocytosis},
author = { J. Carcel-Trullols and C. Aguilar-Gallardo and F. Garcia-Alcalde and M. Angel Pardo-Cea and J. Dopazo and A. Conesa and C. Simon},
url = {http://dx.doi.org/10.1186/2193-1801-1-44},
doi = {10.1186/2193-1801-1-44},
issn = {2193-1801},
year = {2012},
date = {2012-01-01},
journal = {SPRINGERPLUS},
volume = {1},
abstract = {Enforced cell transdifferentiation of human cancer cells is a promising
alternative to conventional chemotherapy. We previously identified
albumin-associated lipid-and, more specifically, saturated fatty
acid-induced transdifferentiation programs in human cancer cells
(HCCLs). In this study, we further characterized the adipocyte-like
cells, resulting from the transdifferentiation of human cancer cell
lines MCF-7 and MALME-3M, and proposed a common mechanistic approach for
these transdifferentiating programs. We showed the loss of pigmentation
in MALME-3M cells treated with albumin-associated lipids, based on
electron microscopic analysis, and the overexpression of perilipin 2
(PLIN2) by western blotting in MALME-3M and MCF-7 cells treated with
unsaturated fatty acids. Comparing the gene expression profiles of naive
melanoma MALME-3M cells and albumin-associated lipid-treated cells, based on RNA sequencing, we confirmed the transcriptional upregulation
of some key adipogenic gene markers and also an alternative splicing of
the adipogenic master regulator PPARG, that is probably related to the
reported up regulated expression of the protein. Most importantly, these
results also showed the upregulation of genes responsible for Clathrin
(CLTC) and other adaptor-related proteins. An increase in CLTC
expression in the transdifferentiated cells was confirmed by western
blotting. Inactivation of CLTC by chlorpromazine (CHP), an inhibitor of
CTLC mediated endocytosis (CME), and gene silencing by siRNAs, partially
reversed the accumulation of neutral lipids observed in the
transdifferentiated cells. These findings give a deeper insight into the
phenotypic changes observed in HCCL to adipocyte-like
transdifferentiation and point towards CME as a key pathway in distinct
transdifferentiation programs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Enforced cell transdifferentiation of human cancer cells is a promising
alternative to conventional chemotherapy. We previously identified
albumin-associated lipid-and, more specifically, saturated fatty
acid-induced transdifferentiation programs in human cancer cells
(HCCLs). In this study, we further characterized the adipocyte-like
cells, resulting from the transdifferentiation of human cancer cell
lines MCF-7 and MALME-3M, and proposed a common mechanistic approach for
these transdifferentiating programs. We showed the loss of pigmentation
in MALME-3M cells treated with albumin-associated lipids, based on
electron microscopic analysis, and the overexpression of perilipin 2
(PLIN2) by western blotting in MALME-3M and MCF-7 cells treated with
unsaturated fatty acids. Comparing the gene expression profiles of naive
melanoma MALME-3M cells and albumin-associated lipid-treated cells, based on RNA sequencing, we confirmed the transcriptional upregulation
of some key adipogenic gene markers and also an alternative splicing of
the adipogenic master regulator PPARG, that is probably related to the
reported up regulated expression of the protein. Most importantly, these
results also showed the upregulation of genes responsible for Clathrin
(CLTC) and other adaptor-related proteins. An increase in CLTC
expression in the transdifferentiated cells was confirmed by western
blotting. Inactivation of CLTC by chlorpromazine (CHP), an inhibitor of
CTLC mediated endocytosis (CME), and gene silencing by siRNAs, partially
reversed the accumulation of neutral lipids observed in the
transdifferentiated cells. These findings give a deeper insight into the
phenotypic changes observed in HCCL to adipocyte-like
transdifferentiation and point towards CME as a key pathway in distinct
transdifferentiation programs.
alternative to conventional chemotherapy. We previously identified
albumin-associated lipid-and, more specifically, saturated fatty
acid-induced transdifferentiation programs in human cancer cells
(HCCLs). In this study, we further characterized the adipocyte-like
cells, resulting from the transdifferentiation of human cancer cell
lines MCF-7 and MALME-3M, and proposed a common mechanistic approach for
these transdifferentiating programs. We showed the loss of pigmentation
in MALME-3M cells treated with albumin-associated lipids, based on
electron microscopic analysis, and the overexpression of perilipin 2
(PLIN2) by western blotting in MALME-3M and MCF-7 cells treated with
unsaturated fatty acids. Comparing the gene expression profiles of naive
melanoma MALME-3M cells and albumin-associated lipid-treated cells, based on RNA sequencing, we confirmed the transcriptional upregulation
of some key adipogenic gene markers and also an alternative splicing of
the adipogenic master regulator PPARG, that is probably related to the
reported up regulated expression of the protein. Most importantly, these
results also showed the upregulation of genes responsible for Clathrin
(CLTC) and other adaptor-related proteins. An increase in CLTC
expression in the transdifferentiated cells was confirmed by western
blotting. Inactivation of CLTC by chlorpromazine (CHP), an inhibitor of
CTLC mediated endocytosis (CME), and gene silencing by siRNAs, partially
reversed the accumulation of neutral lipids observed in the
transdifferentiated cells. These findings give a deeper insight into the
phenotypic changes observed in HCCL to adipocyte-like
transdifferentiation and point towards CME as a key pathway in distinct
transdifferentiation programs.
41.
Leida, C.; Conesa, A.; Llacer, G.; Badenes, M. Luisa; Rios, G.
Histone modifications and expression of DAM6 gene in peach are modulated during bud dormancy release in a cultivar-dependent manner Journal Article
In: NEW PHYTOLOGIST, vol. 193, no. 1, pp. 67-80, 2012, ISSN: 0028-646X.
@article{ISI:000298300800012,
title = {Histone modifications and expression of DAM6 gene in peach are modulated
during bud dormancy release in a cultivar-dependent manner},
author = { C. Leida and A. Conesa and G. Llacer and M. Luisa Badenes and G. Rios},
url = {http://dx.doi.org/10.1111/j.1469-8137.2011.03863.x},
doi = {10.1111/j.1469-8137.2011.03863.x},
issn = {0028-646X},
year = {2012},
date = {2012-01-01},
journal = {NEW PHYTOLOGIST},
volume = {193},
number = {1},
pages = {67-80},
abstract = {Bud dormancy release in many woody perennial plants responds to the
seasonal accumulation of chilling stimulus. MADS-box transcription
factors encoded by DORMANCY ASSOCIATED MADS-box (DAM) genes in peach
(Prunus persica) are implicated in this pathway, but other regulatory
factors remain to be identified. In addition, the regulation of DAM gene
expression is not well known at the molecular level. A microarray
hybridization approach was performed to identify genes whose expression
correlates with the bud dormancy-related behaviour in 10 different peach
cultivars. Histone modifications in DAM6 gene were investigated by
chromatin immunoprecipitation in two different cultivars. The expression
of DAM4DAM6 and several genes related to abscisic acid and drought
stress response correlated with the dormancy behaviour of peach
cultivars. The trimethylation of histone H3 at K27 in the DAM6 promoter, coding region and the second large intron was preceded by a decrease in
acetylated H3 and trimethylated H3K4 in the region of translation start, coinciding with repression of DAM6 during dormancy release. Analysis of
chromatin modifications reinforced the role of epigenetic mechanisms in
DAM6 regulation and bud dormancy release, and highlighted common
features with the vernalization process in Arabidopsis thaliana and
cereals.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bud dormancy release in many woody perennial plants responds to the
seasonal accumulation of chilling stimulus. MADS-box transcription
factors encoded by DORMANCY ASSOCIATED MADS-box (DAM) genes in peach
(Prunus persica) are implicated in this pathway, but other regulatory
factors remain to be identified. In addition, the regulation of DAM gene
expression is not well known at the molecular level. A microarray
hybridization approach was performed to identify genes whose expression
correlates with the bud dormancy-related behaviour in 10 different peach
cultivars. Histone modifications in DAM6 gene were investigated by
chromatin immunoprecipitation in two different cultivars. The expression
of DAM4DAM6 and several genes related to abscisic acid and drought
stress response correlated with the dormancy behaviour of peach
cultivars. The trimethylation of histone H3 at K27 in the DAM6 promoter, coding region and the second large intron was preceded by a decrease in
acetylated H3 and trimethylated H3K4 in the region of translation start, coinciding with repression of DAM6 during dormancy release. Analysis of
chromatin modifications reinforced the role of epigenetic mechanisms in
DAM6 regulation and bud dormancy release, and highlighted common
features with the vernalization process in Arabidopsis thaliana and
cereals.
seasonal accumulation of chilling stimulus. MADS-box transcription
factors encoded by DORMANCY ASSOCIATED MADS-box (DAM) genes in peach
(Prunus persica) are implicated in this pathway, but other regulatory
factors remain to be identified. In addition, the regulation of DAM gene
expression is not well known at the molecular level. A microarray
hybridization approach was performed to identify genes whose expression
correlates with the bud dormancy-related behaviour in 10 different peach
cultivars. Histone modifications in DAM6 gene were investigated by
chromatin immunoprecipitation in two different cultivars. The expression
of DAM4DAM6 and several genes related to abscisic acid and drought
stress response correlated with the dormancy behaviour of peach
cultivars. The trimethylation of histone H3 at K27 in the DAM6 promoter, coding region and the second large intron was preceded by a decrease in
acetylated H3 and trimethylated H3K4 in the region of translation start, coinciding with repression of DAM6 during dormancy release. Analysis of
chromatin modifications reinforced the role of epigenetic mechanisms in
DAM6 regulation and bud dormancy release, and highlighted common
features with the vernalization process in Arabidopsis thaliana and
cereals.
40.
Tarazona, S.; Prado-Lopez, S.; Dopazo, J.; Ferrer, A.; Conesa, A.
Variable selection for multifactorial genomic data Journal Article
In: CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS, vol. 110, no. 1, pp. 113-122, 2012, ISSN: 0169-7439.
@article{ISI:000299712500014,
title = {Variable selection for multifactorial genomic data},
author = { S. Tarazona and S. Prado-Lopez and J. Dopazo and A. Ferrer and A. Conesa},
url = {http://dx.doi.org/10.1016/j.chemolab.2011.10.012},
doi = {10.1016/j.chemolab.2011.10.012},
issn = {0169-7439},
year = {2012},
date = {2012-01-01},
journal = {CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS},
volume = {110},
number = {1},
pages = {113-122},
abstract = {Dimension reduction techniques are used to explore genomic data. Due to
the large number of variables (genes) included in this kind of studies, variable selection methods are needed to identify the most responsive
genes in order to get a better interpretation of the results or to
conduct more specific experiments. These methods should be consistent
with the amount of signal in the data. For this purpose, we introduce a
novel selection strategy called minAS and also adapt other existing
strategies, such us Gamma approximation, resampling techniques, etc. All
of them are based on studying the distribution of statistics measuring
the importance of the variables in the model. These strategies have been
applied to the ASCA-genes analysis framework and more generally to
dimension reduction techniques as PCA. The performance of the different
strategies was evaluated using simulated data. The best performing
methods were then applied on an experimental dataset containing the
transcriptomic profiles of human embryonic stem cells cultured under
different oxygen concentrations. The ability of the methods to extract
relevant biological information from the data is discussed. (C) 2011
Elsevier B.V. All rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Dimension reduction techniques are used to explore genomic data. Due to
the large number of variables (genes) included in this kind of studies, variable selection methods are needed to identify the most responsive
genes in order to get a better interpretation of the results or to
conduct more specific experiments. These methods should be consistent
with the amount of signal in the data. For this purpose, we introduce a
novel selection strategy called minAS and also adapt other existing
strategies, such us Gamma approximation, resampling techniques, etc. All
of them are based on studying the distribution of statistics measuring
the importance of the variables in the model. These strategies have been
applied to the ASCA-genes analysis framework and more generally to
dimension reduction techniques as PCA. The performance of the different
strategies was evaluated using simulated data. The best performing
methods were then applied on an experimental dataset containing the
transcriptomic profiles of human embryonic stem cells cultured under
different oxygen concentrations. The ability of the methods to extract
relevant biological information from the data is discussed. (C) 2011
Elsevier B.V. All rights reserved.
the large number of variables (genes) included in this kind of studies, variable selection methods are needed to identify the most responsive
genes in order to get a better interpretation of the results or to
conduct more specific experiments. These methods should be consistent
with the amount of signal in the data. For this purpose, we introduce a
novel selection strategy called minAS and also adapt other existing
strategies, such us Gamma approximation, resampling techniques, etc. All
of them are based on studying the distribution of statistics measuring
the importance of the variables in the model. These strategies have been
applied to the ASCA-genes analysis framework and more generally to
dimension reduction techniques as PCA. The performance of the different
strategies was evaluated using simulated data. The best performing
methods were then applied on an experimental dataset containing the
transcriptomic profiles of human embryonic stem cells cultured under
different oxygen concentrations. The ability of the methods to extract
relevant biological information from the data is discussed. (C) 2011
Elsevier B.V. All rights reserved.
39.
Yung, S.; Ledran, M.; Moreno-Gimeno, I.; Conesa, A.; Montaner, D.; Dopazo, J.; Dimmick, I.; Slater, N. J.; Marenah, L.; Real, P. J.; Paraskevopoulou, I.; Bisbal, V.; Burks, D.; Santibanez-Koref, M.; Moreno, R.; Mountford, J.; Menendez, P.; Armstrong, L.; Lako, M.
In: HUMAN MOLECULAR GENETICS, vol. 20, no. 24, pp. 4932-4946, 2011, ISSN: 0964-6906.
@article{ISI:000297242100015,
title = {Large-scale transcriptional profiling and functional assays reveal
important roles for Rho-GTPase signalling and SCL during haematopoietic
differentiation of human embryonic stem cells},
author = { S. Yung and M. Ledran and I. Moreno-Gimeno and A. Conesa and D. Montaner and J. Dopazo and I. Dimmick and N. J. Slater and L. Marenah and P. J. Real and I. Paraskevopoulou and V. Bisbal and D. Burks and M. Santibanez-Koref and R. Moreno and J. Mountford and P. Menendez and L. Armstrong and M. Lako},
url = {http://dx.doi.org/10.1093/hmg/ddr431},
doi = {10.1093/hmg/ddr431},
issn = {0964-6906},
year = {2011},
date = {2011-12-01},
journal = {HUMAN MOLECULAR GENETICS},
volume = {20},
number = {24},
pages = {4932-4946},
abstract = {Understanding the transcriptional cues that direct differentiation of
human embryonic stem cells (hESCs) and human-induced pluripotent stem
cells to defined and functional cell types is essential for future
clinical applications. In this study, we have compared transcriptional
profiles of haematopoietic progenitors derived from hESCs at various
developmental stages of a feeder-and serum-free differentiation method
and show that the largest transcriptional changes occur during the first
4 days of differentiation. Data mining on the basis of molecular
function revealed Rho-GTPase signalling as a key regulator of
differentiation. Inhibition of this pathway resulted in a significant
reduction in the numbers of emerging haematopoietic progenitors
throughout the differentiation window, thereby uncovering a previously
unappreciated role for Rho-GTPase signalling during human haematopoietic
development. Our analysis indicated that SCL was the 11th most
upregulated transcript during the first 4 days of the hESC
differentiation process. Overexpression of SCL in hESCs promoted
differentiation to meso-endodermal lineages, the emergence of
haematopoietic and erythro-megakaryocytic progenitors and accelerated
erythroid differentiation. Importantly, intrasplenic transplantation of
SCL-overexpressing hESC-derived haematopoietic cells enhanced recovery
from induced acute anaemia without significant cell engraftment, suggesting a paracrine-mediated effect.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Understanding the transcriptional cues that direct differentiation of
human embryonic stem cells (hESCs) and human-induced pluripotent stem
cells to defined and functional cell types is essential for future
clinical applications. In this study, we have compared transcriptional
profiles of haematopoietic progenitors derived from hESCs at various
developmental stages of a feeder-and serum-free differentiation method
and show that the largest transcriptional changes occur during the first
4 days of differentiation. Data mining on the basis of molecular
function revealed Rho-GTPase signalling as a key regulator of
differentiation. Inhibition of this pathway resulted in a significant
reduction in the numbers of emerging haematopoietic progenitors
throughout the differentiation window, thereby uncovering a previously
unappreciated role for Rho-GTPase signalling during human haematopoietic
development. Our analysis indicated that SCL was the 11th most
upregulated transcript during the first 4 days of the hESC
differentiation process. Overexpression of SCL in hESCs promoted
differentiation to meso-endodermal lineages, the emergence of
haematopoietic and erythro-megakaryocytic progenitors and accelerated
erythroid differentiation. Importantly, intrasplenic transplantation of
SCL-overexpressing hESC-derived haematopoietic cells enhanced recovery
from induced acute anaemia without significant cell engraftment, suggesting a paracrine-mediated effect.
human embryonic stem cells (hESCs) and human-induced pluripotent stem
cells to defined and functional cell types is essential for future
clinical applications. In this study, we have compared transcriptional
profiles of haematopoietic progenitors derived from hESCs at various
developmental stages of a feeder-and serum-free differentiation method
and show that the largest transcriptional changes occur during the first
4 days of differentiation. Data mining on the basis of molecular
function revealed Rho-GTPase signalling as a key regulator of
differentiation. Inhibition of this pathway resulted in a significant
reduction in the numbers of emerging haematopoietic progenitors
throughout the differentiation window, thereby uncovering a previously
unappreciated role for Rho-GTPase signalling during human haematopoietic
development. Our analysis indicated that SCL was the 11th most
upregulated transcript during the first 4 days of the hESC
differentiation process. Overexpression of SCL in hESCs promoted
differentiation to meso-endodermal lineages, the emergence of
haematopoietic and erythro-megakaryocytic progenitors and accelerated
erythroid differentiation. Importantly, intrasplenic transplantation of
SCL-overexpressing hESC-derived haematopoietic cells enhanced recovery
from induced acute anaemia without significant cell engraftment, suggesting a paracrine-mediated effect.