In our previous work, we developed four major bioinformatics tools/databases: (1) the web-based ANOVA-FDR software to provide user-friendly microarray data analysis (http://lgsun.grc.nia.nih.gov/ANOVA/); (2) an algorithm and a fully-automated computational pipeline for transcript assembly from expressed sequences aligned to the mouse genome; (3) a web-based browser to visualize all transcripts and alternative spliced forms of mouse genes (NIA Mouse Gene Index: http://lgsun.grc.nia.nih.gov/geneindex/mm9/); (4) a web-based database and tool to visualize and map the transcription factor binding sites of the mouse genome (CisView: http://lgsun.grc.nia.nih.gov/geneindex/mm6/cisview.html); and (5) a web-based tool to identify consensus sequence motifs based on the genome-wide chromatin-immunoprecipitation coupled with sequencing (ChIP-Seq) method (CisFinder: http: http://lgsun.grc.nia.nih.gov/CisFinder/). We have also developed a new algorithm to simulate the gene expression regulated by two competing transcription factors. Utilizing the bioinformatics tools developed here, we analyzed the global gene expression profiles generated after the overexpression of specific transcriptions factors in mouse ES cells. The analyses helped to identify cis-regulatory elements for both active (i.e., bound by P300, CHD7, mediator, cohesin, and SWI/SNF) or repressed (i.e., with H3K27me3 histone marks and bound by Polycomb factors) states. These results were also used to identify most likely downstream target genes for specific transcription factors. We continued to apply our software tools to various biological problems of our own and in collaboration, which yielded a few publications. We are working constantly to maintain and update the bioinformatics resources that we have developed and made available to the research community. We will continue working on the development of new algorithms and websites for bioinformatics needs. During this reporting period, we have developed a web-based software tool that allows users to carry out comprehensive analyses of gene expression profiling data by uploading their own data or downloading data from the public database, such as GEO. This webtool has been made freely available to the research community.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000702-08
Application #
9147324
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Sharov, Alexei A; Schlessinger, David; Ko, Minoru S H (2015) ExAtlas: An interactive online tool for meta-analysis of gene expression data. J Bioinform Comput Biol 13:1550019
Amano, Tomokazu; Hirata, Tetsuya; Falco, Geppino et al. (2013) Zscan4 restores the developmental potency of embryonic stem cells. Nat Commun 4:1966
Monti, Manuela; Zanoni, Mario; Calligaro, Alberto et al. (2013) Developmental arrest and mouse antral not-surrounded nucleolus oocytes. Biol Reprod 88:2
Livigni, Alessandra; Peradziryi, Hanna; Sharov, Alexei A et al. (2013) A conserved Oct4/POUV-dependent network links adhesion and migration to progenitor maintenance. Curr Biol 23:2233-2244
Hung, Sandy S C; Wong, Raymond C B; Sharov, Alexei A et al. (2013) Repression of global protein synthesis by eif1a-like genes that are expressed specifically in the two-cell embryos and the transient zscan4-positive state of embryonic stem cells. DNA Res 20:391-402
Nishiyama, Akira; Sharov, Alexei A; Piao, Yulan et al. (2013) Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells. Sci Rep 3:1390
Morgani, Sophie M; Canham, Maurice A; Nichols, Jennifer et al. (2013) Totipotent embryonic stem cells arise in ground-state culture conditions. Cell Rep 3:1945-57
Xu, Dongyi; Shen, Weiping; Guo, Rong et al. (2013) Top3? is an RNA topoisomerase that works with fragile X syndrome protein to promote synapse formation. Nat Neurosci 16:1238-47
Yang, Hsih-Te; Ko, Minoru S H (2012) Stochastic modeling for the expression of a gene regulated by competing transcription factors. PLoS One 7:e32376
Sharov, Alexei A; Nishiyama, Akira; Piao, Yulan et al. (2011) Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity. BMC Genomics 12:102

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