Consensus comparative analysis of human embryonic stem cell-derived cardiomyocytes.
Global transcriptional analyses have been performed with human embryonic stem cells (hESC) derived cardiomyocytes (CMs) to identify molecules and pathways important for human CM differentiation, but variations in culture and profiling conditions have led to greatly divergent results among different studies. Consensus investigation to identify genes and gene sets enriched in multiple studies is important for revealing differential gene expression intrinsic to human CM differentiation independent of the above variables, but reliable methods of conducting such comparison are lacking. We examined differential gene expression between hESC and hESC-CMs from multiple microarray studies. For single gene analysis, we identified genes that were expressed at increased levels in hESC-CMs in seven datasets and which have not been previously highlighted. For gene set analysis, we developed a new algorithm, consensus comparative analysis (CSSCMP), capable of evaluating enrichment of gene sets from heterogeneous data sources. Based on both theoretical analysis and experimental validation, CSSCMP is more efficient and less susceptible to experimental variations than traditional methods. We applied CSSCMP to hESC-CM microarray data and revealed novel gene set enrichment (e.g., glucocorticoid stimulus), and also identified genes that might mediate this response. Our results provide important molecular information intrinsic to hESC-CM differentiation. Data and Matlab codes can be downloaded from S1 Data.
Department of Computer Science, Guangzhou University, Guangzhou, P.R. China.
Shaohong
S
Zhang
Stem Cell & Regenerative Medicine Consortium, University of Hong Kong, Hong Kong.
Ellen
E
Poon
Department of Computer Science, Guangzhou University, Guangzhou, P.R. China.
Dongqing
D
Xie
Stem Cell & Regenerative Medicine Consortium, University of Hong Kong, Hong Kong.
Kenneth R
KR
Boheler
Stem Cell & Regenerative Medicine Consortium, University of Hong Kong, Hong Kong.
Ronald A
RA
Li
Department of Computer Science, City University of Hong Kong, Hong Kong.
Hau-San
HS
Wong
D000465:Algorithms; D002454:Cell Differentiation / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D066264:Datasets as Topic; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D015203:Reproducibility of Results