Functional genomics and networks: new approaches in the extraction of complex gene modules

The engine that makes the cell work is made of an intricate network of molecular interactions. Nowadays, the elements and relationships of this complex network can be studied with several types of high-throughput techniques. The dream of having a global picture of the cell from different perspectives that can jointly explain cell behavior is, at least technically, feasible. However, this task can only be accomplished by filling the gap between data and information. The availability of methods capable of accurately managing, integrating and analyzing the results from these experiments is crucial for this purpose. Here, we review the new challenges raised by the availability of different genomic data, as well as the new proposals presented to cope with the increasing data complexity. Special emphasis is given to approaches that explore the transcriptome trying to describe the modules of genes that account for the traits studied.

[1]  Joaquín Dopazo,et al.  Protein Interactions for Functional Genomics , 2012, Int. J. Knowl. Discov. Bioinform..

[2]  E. Fraenkel,et al.  Integrating Proteomic, Transcriptional, and Interactome Data Reveals Hidden Components of Signaling and Regulatory Networks , 2009, Science Signaling.

[3]  Joaquín Dopazo,et al.  SNOW, a web-based tool for the statistical analysis of protein–protein interaction networks , 2009, Nucleic Acids Res..

[4]  Joaquín Dopazo,et al.  Formulating and testing hypotheses in functional genomics , 2009, Artif. Intell. Medicine.

[5]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[6]  Ariel S. Schwartz,et al.  Cost effective strategies for completing the Interactome , 2008, Nature Methods.

[7]  Kenneth H. Buetow,et al.  PID: the Pathway Interaction Database , 2008, Nucleic Acids Res..

[8]  Pooja Mittal,et al.  A novel signaling pathway impact analysis , 2009, Bioinform..

[9]  Taesung Park,et al.  Identification of differentially expressed subnetworks based on multivariate ANOVA , 2009, BMC Bioinformatics.

[10]  J. Dopazo,et al.  Gene set internal coherence in the context of functional profiling , 2009, BMC Genomics.

[11]  Geffrey F. Stopper,et al.  Choosing the right path: enhancement of biologically relevant sets of genes or proteins using pathway structure , 2009, Genome Biology.

[12]  Jeremy Miller,et al.  Identifying disease-specific genes based on their topological significance in protein networks , 2009, BMC Syst. Biol..

[13]  Doheon Lee,et al.  Inferring Pathway Activity toward Precise Disease Classification , 2008, PLoS Comput. Biol..

[14]  Andrea Ciliberto,et al.  Low duplicability and network fragility of cancer genes. , 2008, Trends in genetics : TIG.

[15]  P. Bork,et al.  Drug Target Identification Using Side-Effect Similarity , 2008, Science.

[16]  Hyeong Jun An,et al.  Estimating the size of the human interactome , 2008, Proceedings of the National Academy of Sciences.

[17]  Richard R Copley,et al.  The animal in the genome: comparative genomics and evolution , 2008, Philosophical Transactions of the Royal Society B: Biological Sciences.

[18]  Mirko Francesconi,et al.  Reconstructing networks of pathways via significance analysis of their intersections , 2008, BMC Bioinformatics.

[19]  Wei Pan,et al.  BIOINFORMATICS ORIGINAL PAPER doi:10.1093/bioinformatics/btm612 Systems biology , 2022 .

[20]  Yoshihiro Yamanishi,et al.  KEGG for linking genomes to life and the environment , 2007, Nucleic Acids Res..

[21]  O. Sporns,et al.  Identification and Classification of Hubs in Brain Networks , 2007, PloS one.

[22]  T. Ideker,et al.  Network-based classification of breast cancer metastasis , 2007, Molecular systems biology.

[23]  P. Khatri,et al.  A systems biology approach for pathway level analysis. , 2007, Genome research.

[24]  O. Demin,et al.  The Edinburgh human metabolic network reconstruction and its functional analysis , 2007, Molecular systems biology.

[25]  Sara Linse,et al.  Methods for the detection and analysis of protein–protein interactions , 2007, Proteomics.

[26]  R. Falk,et al.  Approaches for systematic proteome exploration. , 2007, Biomolecular engineering.

[27]  Hongzhe Li,et al.  A Markov random field model for network-based analysis of genomic data , 2007, Bioinform..

[28]  S. Kasif,et al.  Network-Based Analysis of Affected Biological Processes in Type 2 Diabetes Models , 2007, PLoS genetics.

[29]  Jing Zhu,et al.  Edge-based scoring and searching method for identifying condition-responsive protein-protein interaction sub-network , 2007, Bioinform..

[30]  A. Barabasi,et al.  The human disease network , 2007, Proceedings of the National Academy of Sciences.

[31]  Kenneth H. Buetow,et al.  Identification of Key Processes Underlying Cancer Phenotypes Using Biologic Pathway Analysis , 2007, PloS one.

[32]  J. Dopazo,et al.  From genes to functional classes in the study of biological systems , 2007, BMC bioinformatics.

[33]  Jiajun Liu,et al.  Domain-enhanced analysis of microarray data using GO annotations , 2007, Bioinform..

[34]  Peter Bühlmann,et al.  Analyzing gene expression data in terms of gene sets: methodological issues , 2007, Bioinform..

[35]  Monica L. Mo,et al.  Global reconstruction of the human metabolic network based on genomic and bibliomic data , 2007, Proceedings of the National Academy of Sciences.

[36]  Feng Luo,et al.  Modular organization of protein interaction networks , 2007, Bioinform..

[37]  Trey Ideker,et al.  CellCircuits: a database of protein network models , 2006, Nucleic Acids Res..

[38]  J. Tegnér,et al.  Perturbations to uncover gene networks. , 2007, Trends in genetics : TIG.

[39]  F. Bruggeman,et al.  The nature of systems biology. , 2007, Trends in microbiology.

[40]  J. Dopazo,et al.  Evidence for systems-level molecular mechanisms of tumorigenesis , 2007, BMC Genomics.

[41]  Gopal R. Gopinath,et al.  Reactome: a knowledge base of biologic pathways and processes , 2007, Genome Biology.

[42]  Emmanuel Barillot,et al.  Classification of microarray data using gene networks , 2007, BMC Bioinformatics.

[43]  J. Dopazo Functional interpretation of microarray experiments. , 2006, Omics : a journal of integrative biology.

[44]  Yongjin Li,et al.  Discovering disease-genes by topological features in human protein-protein interaction network , 2006, Bioinform..

[45]  A. Barabasi,et al.  A Protein–Protein Interaction Network for Human Inherited Ataxias and Disorders of Purkinje Cell Degeneration , 2006, Cell.

[46]  D. Allison,et al.  Microarray data analysis: from disarray to consolidation and consensus , 2006, Nature Reviews Genetics.

[47]  Jianzhi Zhang,et al.  Why Do Hubs Tend to Be Essential in Protein Networks? , 2006, PLoS genetics.

[48]  K. N. Chandrika,et al.  Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasets , 2006, Nature Genetics.

[49]  John D. Storey,et al.  A network-based analysis of systemic inflammation in humans , 2005, Nature.

[50]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[51]  Purvesh Khatri,et al.  Ontological analysis of gene expression data: current tools, limitations, and open problems , 2005, Bioinform..

[52]  Jun Lu,et al.  Pathway level analysis of gene expression using singular value decomposition , 2005, BMC Bioinformatics.

[53]  Martin Kuiper,et al.  BiNGO: a Cytoscape plugin to assess overrepresentation of Gene Ontology categories in Biological Networks , 2005, Bioinform..

[54]  Joaquín Dopazo,et al.  Discovering molecular functions significantly related to phenotypes by combining gene expression data and biological information , 2005, Bioinform..

[55]  Stanley N Cohen,et al.  Effects of threshold choice on biological conclusions reached during analysis of gene expression by DNA microarrays. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[56]  T. Ideker,et al.  Systematic interpretation of genetic interactions using protein networks , 2005, Nature Biotechnology.

[57]  Andrew B. Nobel,et al.  Significance analysis of functional categories in gene expression studies: a structured permutation approach , 2005, Bioinform..

[58]  R. Karp,et al.  From the Cover : Conserved patterns of protein interaction in multiple species , 2005 .

[59]  Jason A. Papin,et al.  Reconstruction of cellular signalling networks and analysis of their properties , 2005, Nature Reviews Molecular Cell Biology.

[60]  Seon-Young Kim,et al.  PAGE: Parametric Analysis of Gene Set Enrichment , 2005, BMC Bioinform..

[61]  Thomas J. Begley,et al.  Global network analysis of phenotypic effects: Protein networks and toxicity modulation in Saccharomyces cerevisiae , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[62]  Lambert C. J. Dorssers,et al.  GO-Mapper: functional analysis of gene expression data using the expression level as a score to evaluate Gene Ontology terms , 2004, Bioinform..

[63]  E. Lander,et al.  Finishing the euchromatic sequence of the human genome , 2004 .

[64]  C. Ponting,et al.  Finishing the euchromatic sequence of the human genome , 2004 .

[65]  H. Brunner,et al.  From syndrome families to functional genomics , 2004, Nature Reviews Genetics.

[66]  Homin K. Lee,et al.  Coexpression analysis of human genes across many microarray data sets. , 2004, Genome research.

[67]  R. Milo,et al.  Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[68]  Joaquín Dopazo,et al.  FatiGO: a web tool for finding significant associations of Gene Ontology terms with groups of genes , 2004, Bioinform..

[69]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[70]  Anton J. Enright,et al.  Detection of functional modules from protein interaction networks , 2003, Proteins.

[71]  Dennis M. Wilkinson,et al.  A method for finding communities of related genes , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[72]  International Human Genome Sequencing Consortium Finishing the euchromatic sequence of the human genome , 2004 .

[73]  Thomas Lengauer,et al.  Statistical Applications in Genetics and Molecular Biology Calculating the Statistical Significance of Changes in Pathway Activity From Gene Expression Data , 2011 .

[74]  Jelle J. Goeman,et al.  A global test for groups of genes: testing association with a clinical outcome , 2004, Bioinform..

[75]  Susumu Goto,et al.  The KEGG resource for deciphering the genome , 2004, Nucleic Acids Res..

[76]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[77]  Joshua M. Stuart,et al.  A Gene-Coexpression Network for Global Discovery of Conserved Genetic Modules , 2003, Science.

[78]  M. Daly,et al.  PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes , 2003, Nature Genetics.

[79]  Purvesh Khatri,et al.  Onto-Tools, the toolkit of the modern biologist: Onto-Express, Onto-Compare, Onto-Design and Onto-Translate , 2003, Nucleic Acids Res..

[80]  E. Sonnhammer,et al.  Genomic gene clustering analysis of pathways in eukaryotes. , 2003, Genome research.

[81]  Alexander Rives,et al.  Modular organization of cellular networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[82]  May D. Wang,et al.  GoMiner: a resource for biological interpretation of genomic and proteomic data , 2003, Genome Biology.

[83]  M. Gerstein,et al.  Systematic learning of gene functional classes from DNA array expression data by using multilayer perceptrons. , 2002, Genome research.

[84]  Nicola J. Rinaldi,et al.  Transcriptional Regulatory Networks in Saccharomyces cerevisiae , 2002, Science.

[85]  N. Katsanis,et al.  Human genetics and disease: Beyond Mendel: an evolving view of human genetic disease transmission , 2002, Nature Reviews Genetics.

[86]  Benno Schwikowski,et al.  Discovering regulatory and signalling circuits in molecular interaction networks , 2002, ISMB.

[87]  Daniel Hanisch,et al.  Co-clustering of biological networks and gene expression data , 2002, ISMB.

[88]  H. Kitano Systems Biology: A Brief Overview , 2002, Science.

[89]  M E J Newman,et al.  Community structure in social and biological networks , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[90]  Kathy Chen,et al.  Network dynamics and cell physiology , 2001, Nature Reviews Molecular Cell Biology.

[91]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[92]  J. Hopfield,et al.  From molecular to modular cell biology , 1999, Nature.

[93]  Albert,et al.  Emergence of scaling in random networks , 1999, Science.

[94]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[95]  Edsger W. Dijkstra,et al.  A note on two problems in connexion with graphs , 1959, Numerische Mathematik.