Unraveling transcriptional regulatory programs by integrative analysis of microarray and transcription factor binding data

Huai Li, Ming Zhan


Unraveling the transcriptional regulatory program mediated by transcription factors (TFs) is a fundamental objective of computational biology, yet still remains a challenge. Here, we present a new methodology that integrates microarray and TF binding data for unraveling transcriptional regulatory networks. The algorithm is based on a two-stage constrained matrix decomposition model. The model takes into account the non-linear structure in gene expression data, particularly in the TF-target gene interactions and the combinatorial nature of gene regulation by TFs. The gene expression profile is modeled as a linear weighted combination of the activity profiles of a set of TFs. The TF activity profiles are deduced from the expression levels of TF target genes, instead directly from TFs themselves. The TF-target gene relationships are derived from ChIP-chip and other TF binding data. The proposed algorithm can not only identify transcriptional modules, but also reveal regulatory programs of which TFs control which target genes in which specific ways (either activating or inhibiting). In comparison with other methods, our algorithm identifies biologically more meaningful transcriptional modules relating to specific TFs. We applied th...Continue Reading

Associated Proceedings Papers

Aug 24, 2018·Teresa W-M. FanYi Zhang


Aug 24, 2010·Omics : a Journal of Integrative Biology·Mojca MattiazziUros Petrovic
Nov 5, 2010·Science Translational Medicine·Nicholas F Marko, Robert J Weil
Dec 8, 2009·BMC Bioinformatics·Cheng-Long ChuangGrace S Shieh
Apr 1, 2010·BMC Bioinformatics·Chen WangRobert Clarke
Aug 28, 2009·PloS One·Scott ChristleyXiaohui Xie
Dec 15, 2010·PloS One·Adrian SchröderAndreas Zell
Nov 19, 2013·BMC Genomics·Shan ZhongZiv Bar-Joseph
Sep 14, 2010·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Duccio Cavalieri
Jul 14, 2010·Journal of Biomedical Informatics·Jesse M EngreitzRuss B Altman
Dec 18, 2013·EURASIP Journal on Bioinformatics & Systems Biology·Bin Jia, Xiaodong Wang
Oct 24, 2014·PLoS Computational Biology·Yue LiZhaolei Zhang
Jan 20, 2010·Trends in Genetics : TIG·Matthew T Weirauch, Timothy R Hughes
Jun 28, 2012·PLoS Computational Biology·Theresa NiederbergerAchim Tresch
Jun 1, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cuong Chieu To, Jiri Vohradsky
Feb 9, 2010·Bioinformatics and Biology Insights·Haoyu ChengQi Liu
Dec 5, 2017·The Journal of Clinical Investigation·Liying ChenKimberly Stegmaier


Oct 29, 1997·Molecular and Cellular Biology·D H SweetG B Sancar
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·M B EisenD Botstein
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·Pablo TamayoTodd R Golub
Jul 3, 1999·Nature Genetics·S TavazoieG M Church
Aug 18, 2000·Neural Networks : the Official Journal of the International Neural Network Society·A Hyvärinen, E Oja
Aug 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·O AlterD Botstein
Dec 5, 2000·Molecular Biology of the Cell·A P GaschP Brown
Jun 8, 2001·Bioinformatics·O TroyanskayaRuss B Altman
Feb 12, 2002·Bioinformatics·Wolfram Liebermeister
Oct 14, 2003·Nature Biotechnology·Ziv Bar-JosephDavid K Gifford
Oct 16, 2003·Genome Research·Markus J HerrgårdBernhard Ø Palsson
Nov 13, 2003·Genome Biology·Su-In Lee, Serafim Batzoglou
Dec 16, 2003·Proceedings of the National Academy of Sciences of the United States of America·James C LiaoVwani P Roychowdhury
Mar 16, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jean-Philippe BrunetJill P Mesirov
Sep 3, 2004·Nature·Christopher T HarbisonRichard A Young
Sep 28, 2004·Nature Genetics·Eran SegalAviv Regev
Dec 14, 2004·International Journal of Neural Systems·Christian Jutten, Juha Karhunen
Jan 18, 2005·Nature Biotechnology·Xianghong Jasmine ZhouWing Hung Wong
Sep 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Huai-Kuang TsaiWen-Hsiung Li
May 9, 2006·Genome Biology·Karen LemmensKathleen Marchal
Aug 5, 2006·Methods in Molecular Biology·Jeremy GollubGavin Sherlock
Jan 6, 2007·Genome Biology·Guang ChenChristian J Stoeckert
May 29, 2007·Nucleic Acids Research·Christina BackesHans-Peter Lenhof
Feb 7, 2008·IEEE Transactions on Neural Networks·J Nie, S Haykin

Related Concepts

In Silico
Microarray Analysis
Biological Adaptation to Stress
Transcription, Genetic
Candidate Disease Gene
Gene Expression
Protein Interaction Mapping
Systems Integration
Transcription Factor Binding
Cell Cycle

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Sexual Dimorphism in Neurodegeneration

There exist sex differences in neurodevelopmental and neurodegenerative disorders. For instance, multiple sclerosis is more common in women, whereas Parkinson’s disease is more common in men. Here is the latest research on sexual dimorphism in neurodegeneration

HLA Genetic Variation

HLA genetic variation has been found to confer risk for a wide variety of diseases. Identifying these associations and understanding their molecular mechanisms is ongoing and holds promise for the development of therapeutics. Find the latest research on HLA genetic variation here.

Super-resolution Microscopy

Super-resolution microscopy is the term commonly given to fluorescence microscopy techniques with resolutions that are not limited by the diffraction of light. Here are the latest discoveries pertaining to super-resolution microscopy.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.

Brain Lower Grade Glioma

Low grade gliomas in the brain form from oligodendrocytes and astrocytes and are the slowest-growing glioma in adults. Discover the latest research on these brain tumors here.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
James C LiaoVwani P Roychowdhury
Journal of Computational Biology : a Journal of Computational Molecular Cell Biology
Nir FriedmanD Pe'er
Fantine Mordelet, Jean-Philippe Vert
© 2020 Meta ULC. All rights reserved