CSCI2951-N: Advanced Algorithms in Computational Biology http://www.cs.brown.edu/courses/csci2951-n/

Prof. Sorin Istrail

Published Genome-Wide Associations through 20111,617 published GWA at p≤5X10-8 for 249 traits

Autism marker Multiple Sclerosis Marker

The GWAS Human Genome

Published Genome-Wide Associations through 20111,617 published GWA at p≤5X10-8 for 249 traits

Genetic Heterogeneity

The Common Disease Common Variant (CDCV) hypothesis is dead. Long live the Common Disease Many Rare Variants hypothesis!

The CDCV ‘s classical drawing metaphor as “Needles in the Haystack,” with few needles with a common look in a large haystack, needs to be replaced now with a van Gogh-like drawing, with many needles each differently looking and private to areas in the large haystack.

Vincent

CSCI2951-N: Advanced Algorithms in Computational Biology http://www.cs.brown.edu/courses/csci2951-n/

Prof. Sorin Istrail

The GWAS Human Genome

Published Genome-Wide Associations through 20111,617 published GWA at p≤5X10-8 for 249 traits

The Missing Heritability Puzzle

Additivity of alleles? Just a convenient approximation, friendly to “heritability” measured as a correlation coefficient.

Ronald

CSCI2951-N: Advanced Algorithms in Computational Biology http://www.cs.brown.edu/courses/csci2951-n/

Prof. Sorin Istrail

The GWAS Human Genome

Published Genome-Wide Associations through 20111,617 published GWA at p≤5X10-8 for 249 traits

• haplotype phasing, linkage disequilibrium, tagging SNPs, identical by descent (IBD), pedigrees, trios

• coalescent theory, Polya urn game, Ewens sampling lemma, genome-wide graph theory algorithms

• the genetic heterogeneity problem, the missing heritability problem

• statistical models of disease, association tests and multiple hypothesis testing

• autism, multiple sclerosis, type 2 diabetes

Application Topics include

CSCI2951-N: Advanced Algorithms in Computational Biology http://www.cs.brown.edu/courses/csci2951-n/

Prof. Sorin Istrail

The GWAS Human Genome

Genomic Foundations

• Modeling and Measuring Evolution: Linkage Disequilibrium (LD), Urn Models

• Genome-Wide Association Studies (GWAS): Statistical associations, the missing heritabililty problem, genetic heterogeneity, genomic privacy

Algorithms

• Maximum Likelihood and Expectation-Maximization Algorithms Biological Problem: Inferring haplotype frequencies in populations.

• Set-cover and Minimum Informative Subset Algorithms Biological Problem: Tagging SNPs selection, LD.

Algorithms

• Markov Chain Monte Carlo Algorithms Biological Problem: Population Substructure

• Knapsack Algorithms and Statistical Hypothesis Testing, The Neyman-Pearson Lemma, Multiple Testing Biological Problem: Statistical Associations in GWAS

Algorithms

• Voting Theory Algorithms, von Neumann-Morgenstern Utility Theory & The Social Network of Protein Folds

Biological Problem: The Protein Folding Problem - Individual Preferences of Amino Acids and the Thermodynamic "Social Choice" Hypothesis - The Protein Folding Energy Function Inference Problem