[Apologies for multiple postings]

This is just a reminder. Yoo-Ah Kim from NIH will
give a talk at tomorrow noon (Tuesday). Please
see details below.

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*    GRAND Seminar
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*    http://cs.gmu.edu/~robotics/Main/GrandSeminar
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*Title*

Identifying Causal Genes and Dysregulated Pathways
in Complex Diseases


*Time/Venue*

CS conference room, ENGR 4201
Noon, November 1, Tue.

*Speaker*

Yoo-Ah Kim
Research Fellow
National Center for Biotechnology Information (NCBI)
National Institutes of Health

*Host*

Jyh-Ming Lien

*Abstract*

In complex diseases various combinations of genomic
perturbations often lead to the same phenotype. On a
molecular level, combinations of genomic perturbations
potentially dys-regulate the same important cellular
pathways. Such pathway-centric perspective is fundamental to
understanding the mechanisms of complex diseases and the
identification of potential drug targets. While previous
methods have given valuable insight into the modular nature
of diseases, they did not provide a genome-wide view on
possible effectors of such dys-regulation.In order to
provide an integrated perspective on complex disease
mechanisms, we developed a novel computational method to
simultaneously identify causal genes and dys-regulated
pathways.

For the first step, we identified a representative set of
genes that are differentially expressed in cancer and
control. Assuming that diseases associated gene expression
changes are in large extend caused by genomic alterations,
we then determined potential paths from such genomic causes
to target genes through a network of molecular interactions.
Applying our method to sets of genomic alterations and gene
expression profiles of 158 Glioblastoma multiforme (GBM)
patients we uncovered candidate causal genes and causal
paths that are potentially responsible for the altered
expression of disease genes. As expected, we found a number
of causal genes in the large areas of genomic alteration on
chromosomes 7 and 10, coinciding with the genomic locations
of EGFR and PTEN. In addition, we discovered other putative
causal genes that potentially play a role in the disease.
Our method combines Quantitative Trait Loci (eQTL) analysis
with pathway information resulting in a very powerful
approach which allows to identify potential causal genes as
well as intermediate nodes on molecular pathways that
mediate information flow between causal and target genes.
While copy number variation and gene expression data of
glioblastoma patients provided opportunities to test our
approach, our method can be applied to any disease system
where genetic variations play a fundamental causal role.

Short bio:

Yoo-Ah Kim is a Research Fellow in the National Center for
Biotechnology Information (NCBI) at the National Institutes
of Health. Before joining NCBI, she received her PhD degree
in Computer Science from the University of Maryland in 2005
and was a faculty member in the department of Computer
Engineering at the University of Connecticut from 2005 to
2009.


-- 
*Jyh-Ming Lien*
Assistant Professor, George Mason University
+1-703-993-9546
http://cs.gmu.edu/~jmlien