1. Scientific Reports
- Author
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Zhen Zhang, David M. Herrington, Lulu Chen, Eric P. Hoffman, Chunyu Liu, Guoqiang Yu, Yue Wang, Robert Clarke, Niya Wang, Li Chen, and Electrical and Computer Engineering
- Subjects
0301 basic medicine ,separation ,In silico ,cycle-regulated genes ,brain ,Genes, Fungal ,Computational biology ,Brain tissue ,Biology ,Models, Biological ,Article ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Tissue heterogeneity ,Yeasts ,Gene expression ,Animals ,cancer ,patterns ,Gene ,Lung ,Genetics ,Multidisciplinary ,Small number ,Gene Expression Profiling ,expression deconvolution ,Brain ,tool ,Rats ,Gene expression profiling ,030104 developmental biology ,Liver ,cell-cycle ,Organ Specificity ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Tissue heterogeneity is both a major confounding factor and an underexploited information source. While a handful of reports have demonstrated the potential of supervised computational methods to deconvolute tissue heterogeneity, these approaches require a priori information on the marker genes or composition of known subpopulations. To address the critical problem of the absence of validated marker genes for many (including novel) subpopulations, we describe convex analysis of mixtures (CAM), a fully unsupervised in silico method, for identifying subpopulation marker genes directly from the original mixed gene expressions in scatter space that can improve molecular analyses in many biological contexts. Validated with predesigned mixtures, CAM on the gene expression data from peripheral leukocytes, brain tissue, and yeast cell cycle, revealed novel marker genes that were otherwise undetectable using existing methods. Importantly, CAM requires no a priori information on the number, identity, or composition of the subpopulations present in mixed samples, and does not require the presence of pure subpopulations in sample space. This advantage is significant in that CAM can achieve all of its goals using only a small number of heterogeneous samples, and is more powerful to distinguish between phenotypically similar subpopulations. National Institutes of Health [NS029525, CA160036, CA184902, ES024988, CA149653, HL111362] This work was funded in part by the National Institutes of Health under Grants NS029525, CA160036, CA184902, ES024988, CA149653, and HL111362.
- Published
- 2016