MCbiclust: a novel algorithm to discover large-scale functionally related gene sets from massive transcriptomics data collections

被引:9
作者
Bentham, Robert B. [1 ,2 ]
Bryson, Kevin [3 ]
Szabadkai, Gyorgy [1 ,2 ,4 ]
机构
[1] UCL, Dept Cell & Dev Biol, Consortium Mitochondrial Res, London WC1E 6BT, England
[2] Francis Crick Inst, London NW1 1AT, England
[3] UCL, Dept Comp Sci, London WC1E 6BT, England
[4] Univ Padua, Dept Biomed Sci, I-35131 Padua, Italy
基金
英国惠康基金;
关键词
BICLUSTERING METHOD; EXPRESSION; CANCER; NETWORKS; REDOX;
D O I
10.1093/nar/gkx590
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The potential to understand fundamental biological processes from gene expression data has grown in parallel with the recent explosion of the size of data collections. However, to exploit this potential, novel analytical methods are required, capable of discovering large co-regulated gene networks. We found current methods limited in the size of correlated gene sets they could discover within biologically heterogeneous data collections, hampering the identification of multi-gene controlled fundamental cellular processes such as energy metabolism, organelle biogenesis and stress responses. Here we describe a novel biclustering algorithm called Massively Correlated Biclustering (MCbiclust) that selects samples and genes from large datasets with maximal correlated gene expression, allowing regulation of complex networks to be examined. The method has been evaluated using synthetic data and applied to large bacterial and cancer cell datasets. We show that the large biclusters discovered, so far elusive to identification by existing techniques, are biologically relevant and thus MCbiclust has great potential in the analysis of transcriptomics data to identify large-scale unknown effects hidden within the data. The identified massive biclusters can be used to develop improved transcriptomics based diagnosis tools for diseases caused by altered gene expression, or used for further network analysis to understand genotype-phenotype correlations.
引用
收藏
页码:8712 / 8730
页数:19
相关论文
共 66 条
[51]   Mitonuclear communication in homeostasis and stress [J].
Quiros, Pedro M. ;
Mottis, Adrienne ;
Auwerx, Johan .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2016, 17 (04) :213-226
[52]   g:Profiler-a web server for functional interpretation of gene lists (2016 update) [J].
Reimand, Juri ;
Arak, Tambet ;
Adler, Priit ;
Kolberg, Liis ;
Reisberg, Sulev ;
Peterson, Hedi ;
Vilo, Jaak .
NUCLEIC ACIDS RESEARCH, 2016, 44 (W1) :W83-W89
[53]   SILHOUETTES - A GRAPHICAL AID TO THE INTERPRETATION AND VALIDATION OF CLUSTER-ANALYSIS [J].
ROUSSEEUW, PJ .
JOURNAL OF COMPUTATIONAL AND APPLIED MATHEMATICS, 1987, 20 :53-65
[54]   Antibiotic-Induced Replication Stress Triggers Bacterial Competence by Increasing Gene Dosage near the Origin [J].
Slager, Jelle ;
Kjos, Morten ;
Attaiech, Laetitia ;
Veening, Jan-Willem .
CELL, 2014, 157 (02) :395-406
[55]   BioGRID: a general repository for interaction datasets [J].
Stark, Chris ;
Breitkreutz, Bobby-Joe ;
Reguly, Teresa ;
Boucher, Lorrie ;
Breitkreutz, Ashton ;
Tyers, Mike .
NUCLEIC ACIDS RESEARCH, 2006, 34 :D535-D539
[56]   Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles [J].
Subramanian, A ;
Tamayo, P ;
Mootha, VK ;
Mukherjee, S ;
Ebert, BL ;
Gillette, MA ;
Paulovich, A ;
Pomeroy, SL ;
Golub, TR ;
Lander, ES ;
Mesirov, JP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (43) :15545-15550
[57]   STRING v10: protein-protein interaction networks, integrated over the tree of life [J].
Szklarczyk, Damian ;
Franceschini, Andrea ;
Wyder, Stefan ;
Forslund, Kristoffer ;
Heller, Davide ;
Huerta-Cepas, Jaime ;
Simonovic, Milan ;
Roth, Alexander ;
Santos, Alberto ;
Tsafou, Kalliopi P. ;
Kuhn, Michael ;
Bork, Peer ;
Jensen, Lars J. ;
von Mering, Christian .
NUCLEIC ACIDS RESEARCH, 2015, 43 (D1) :D447-D452
[58]  
Tanay Amos, 2002, Bioinformatics, V18 Suppl 1, pS136
[59]   Predicting Metabolic Fluxes Using Gene Expression Differences As Constraints [J].
van Berlo, Rogier J. P. ;
de Ridder, Dick ;
Daran, Jean-Marc ;
Daran-Lapujade, Pascale A. S. ;
Teusink, Bas ;
Reinders, Marcel J. T. .
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS, 2011, 8 (01) :206-216
[60]  
van der Maaten L, 2008, J MACH LEARN RES, V9, P2579