NDLI: A system for enhancing genome-wide coexpression dynamics study

Content Provider	PubMed Central
Author	Li, Ker-chau Liu, Ching-ti Sun, Wei Yuan, Shinsheng Yu, Tianwei
Copyright Year	2004
Abstract	Statistical similarity analysis has been instrumental in elucidation of the voluminous microarray data. Genes with correlated expression profiles tend to be functionally associated. However, the majority of functionally associated genes turn out to be uncorrelated. One conceivable reason is that the expression of a gene can be sensitively dependent on the often-varying cellular state. The intrinsic state change has to be plastically accommodated by gene-regulatory mechanisms. To capture such dynamic coexpression between genes, a concept termed “liquid association” (LA) has been introduced recently. LA offers a scoring system to guide a genome-wide search for critical cellular players that may interfere with the coexpression of a pair of genes, thereby weakening their overall correlation. Although the LA method works in many cases, a direct extension to more than two genes is hindered by the “curse of dimensionality.” Here we introduce a strategy of finding an informative 2D projection to generalize LA for multiple genes. A web site is constructed that performs on-line LA computation for any user-specified group of genes. We apply this scoring system to study yeast protein complexes by using the Saccharomyces cerevisiae protein complexes database of the Munich Information Center for Protein Sequences. Human genes are also investigated by profiling of 60 cancer cell lines of the National Cancer Institute. In particular, our system links the expression of the Alzheimer's disease hallmark gene APP (amyloid-β precursor protein) to the β-site-cleaving enzymes BACE and BACE2, the γ-site-cleaving enzymes presenilin 1 and 2, apolipoprotein E, and other Alzheimer's disease-related genes.
Related Links	http://dx.doi.org/10.1073/pnas.0402962101
Starting Page	15561
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	44
Volume Number	101
Language	English
Publisher	National Academy of Sciences
Publisher Date	2004-11-02
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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