Publications

@article{ISI:000343030500001,

title = {Assessing technical performance in differential gene expression 

experiments with external spike-in RNA control ratio mixtures},

author = { S. A. Munro and S. P. Lund and P. S. Pine and H. Binder and D. Clevert and A. Conesa and J. Dopazo and M. Fasold and S. Hochreiter and H. Hong and N. Jafari and D. P. Kreil and P. P. Labaj and S. Li and Y. Liao and S. M. Lin and J. Meehan and C. E. Mason and J. Santoyo-Lopez and R. A. Setterquist and L. Shi and W. Shi and G. K. Smyth and N. Stralis-Pavese and Z. Su and W. Tong and C. Wang and J. Wang and J. Xu and Z. Ye and Y. Yang and Y. Yu and M. Salit},

url = {http://dx.doi.org/10.1038/ncomms6125},

doi = {10.1038/ncomms6125},

issn = {2041-1723},

year  = {2014},

date = {2014-09-01},

journal = {NATURE COMMUNICATIONS},

volume = {5},

abstract = {There is a critical need for standard approaches to assess, report and 

compare the technical performance of genome-scale differential gene 

expression experiments. Here we assess technical performance with a 

proposed standard `dashboard' of metrics derived from analysis of 

external spike-in RNA control ratio mixtures. These control ratio 

mixtures with defined abundance ratios enable assessment of diagnostic 

performance of differentially expressed transcript lists, limit of 

detection of ratio (LODR) estimates and expression ratio variability and 

measurement bias. The performance metrics suite is applicable to 

analysis of a typical experiment, and here we also apply these metrics 

to evaluate technical performance among laboratories. An interlaboratory 

study using identical samples shared among 12 laboratories with three 

different measurement processes demonstrates generally consistent 

diagnostic power across 11 laboratories. Ratio measurement variability 

and bias are also comparable among laboratories for the same measurement 

process. We observe different biases for measurement processes using 

different mRNA-enrichment protocols.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ISI:000351589702079,

title = {Differentially expressed functions and genes between serrated 

adenocarcinoma and sporadic colorectal carcinoma showing histological 

and molecular features of high level of microsatellite instability},

author = { M. Turpin Sevilla and R. Carbonell-Munoz and J. Garcia-Solano and D. Torres-Moreno and F. Garcia-Garcia and A. Conesa and M. Perez-Guillermo and P. Conesa-Zamora},

issn = {0959-8049},

year  = {2014},

date = {2014-07-01},

journal = {EUROPEAN JOURNAL OF CANCER},

volume = {50},

number = {5},

pages = {S219},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ISI:000338246200001,

title = {Relationship between genome and epigenome - challenges and requirements 

for future research},

author = { G. Almouzni and L. Altucci and B. Amati and N. Ashley and D. Baulcombe and N. Beaujean and C. Bock and E. Bongcam-Rudloff and J. Bousquet and S. Braun and B. Bressac-de Paillerets and M. Bussemakers and L. Clarke and A. Conesa and X. Estivill and A. Fazeli and N. Grgurevic and I. Gut and B. T. Heijmans and S. Hermouet and J. Houwing-Duistermaat and I. Iacobucci and J. Ilas and R. Kandimalla and S. Krauss-Etschmann and P. Lasko and S. Lehmann and A. Lindroth and G. Majdic and E. Marcotte and G. Martinelli and N. Martinet and E. Meyer and C. Miceli and K. Mills and M. Moreno-Villanueva and G. Morvan and D. Nickel and B. Niesler and M. Nowacki and J. Nowak and S. Ossowski and M. Pelizzola and R. Pochet and U. Potocnik and M. Radwanska and J. Raes and M. Rattray and M. D. Robinson and B. Roelen and S. Sauer and D. Schinzer and E. Slagboom and T. Spector and H. G. Stunnenberg and E. Tiligada and M. Torres-Padilla and R. Tsonaka and A. Van Soom and M. Vidakovic and M. Widschwendter},

url = {http://dx.doi.org/10.1186/1471-2164-15-487},

doi = {10.1186/1471-2164-15-487},

issn = {1471-2164},

year  = {2014},

date = {2014-06-01},

journal = {BMC GENOMICS},

volume = {15},

abstract = {Understanding the links between genetic, epigenetic and non-genetic 

factors throughout the lifespan and across generations and their role in 

disease susceptibility and disease progression offer entirely new 

avenues and solutions to major problems in our society. To overcome the 

numerous challenges, we have come up with nine major conclusions to set 

the vision for future policies and research agendas at the European 

level.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ISI:000333499100007,

title = {Sequencing and functional analysis of the genome of a nematode 

egg-parasitic fungus, Pochonia chlamydosporia},

author = { E. Larriba and M. D. L. A. Jaime and J. Carbonell-Caballero and A. Conesa and J. Dopazo and C. Nislow and J. Martin-Nieto and L. Vicente Lopez-Llorca},

url = {http://dx.doi.org/10.1016/j.fgb.2014.02.002},

doi = {10.1016/j.fgb.2014.02.002},

issn = {1087-1845},

year  = {2014},

date = {2014-04-01},

journal = {FUNGAL GENETICS AND BIOLOGY},

volume = {65},

pages = {69-80},

abstract = {Pochonia chlamydosporia is a worldwide-distributed soil fungus with a 

great capacity to infect and destroy the eggs and kill females of 

plant-parasitic nematodes. Additionally, it has the ability to colonize 

endophytically roots of economically-important crop plants, thereby 

promoting their growth and eliciting plant defenses. This multitrophic 

behavior makes P. chlamydosporia a potentially useful tool for 

sustainable agriculture approaches. We sequenced and assembled similar 

to 41 Mb of P. chlamydosporia genomic DNA and predicted 12,122 gene 

models, of which many were homologous to genes of fungal pathogens of 

invertebrates and fungal plant pathogens. Predicted genes (65%) were 

functionally annotated according to Gene Ontology, and 16% of them 

found to share homology with genes in the Pathogen Host Interactions 

(PHI) database. The genome of this fungus is highly enriched in genes 

encoding hydrolytic enzymes, such as proteases, glycoside hydrolases and 

carbohydrate esterases. We used RNA-Seq technology in order to identify 

the genes expressed during endophytic behavior of P. chlamydosporia when 

colonizing barley roots. Functional annotation of these genes showed 

that hydrolytic enzymes and transporters are expressed during 

endophytism. This structural and functional analysis of the P. 

chlamydosporia genome provides a starting point for understanding the 

molecular mechanisms involved in the multitrophic lifestyle of this 

fungus. The genomic information provided here should also prove useful 

for enhancing the capabilities of this fungus as a biocontrol agent of 

plant-parasitic nematodes and as a plant growth-promoting organism. (C) 

2014 Elsevier Inc. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ISI:000331407000009,

title = {Molecular interactions between sugar beet and Polymyxa betae during its 

life cycle},

author = { N. Desoignies and J. Carbonell and J. -S. Moreau and A. Conesa and J. Dopazo and A. Legreve},

url = {http://dx.doi.org/10.1111/aab.12095},

doi = {10.1111/aab.12095},

issn = {0003-4746},

year  = {2014},

date = {2014-03-01},

journal = {ANNALS OF APPLIED BIOLOGY},

volume = {164},

number = {2},

pages = {244-256},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}

@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}

}