Luke Alden Yancy, Jr.Mentor: Robert Riley

Broad Institute of MIT & HarvardCambridge, MA

Source: http://staff.vbi.vt.edu/pathport/pathinfo_images/Mycobacterium_tuberculosis/AerosolTransmission.jpg

Source: WHO Stop TB Department, website: www.who.int/tb

Deaths Causes by TB (Estimated by WHO)

1998 1,751,858

2006 1,654,805

Learn more about Mycobacterium Tuberculosis (Mtb) using analysis of gene expression data

Biclustering◦ Bimax (Prelic et al. 2006)◦ CC (Cheng and Church, 2000)◦ Plaid Model (Turner et al.

2003)◦ Spectral (Kluger et al. 2003)◦ Xmotifs (Murali and Kasif,

2003)

Traditional Clustering◦ K-Means (MacQueen, 1967)◦ Hierarchical (Eisen et al. 1998)

Traditional Clustering

Biclustering

Gene Clusters Based on:

All Experiments Subsets of Experiments

Genes Assigned to Clusters:

One-to-OneMany-to-Many/ One-to-

Many

Reproducibility: YesNo (due to random steps in algorithm)

Source: Machine Learning and Its Applications to Biology, Tarca et al. 2007. (Editor: Fran Lewitter, Whitehead Institute)

Bimax K-Means

Boshoff Data(Processed: 3924 Genes, 359

Experiments)

Clusters of Genes

Source: The Transcriptional Responses of Mycobacterium tuberculosis to Inhibitors of Metabolism. (Boshoff et al. 2004)

(Source: http://www.nature.com/nature/journal/v409/n6823/full/4091007a0.html)

(proS loci of Mtb )

Cluster Operon

Gene Pair

(k)

(N)

(m) (n)

Significance of overlap k estimated using hypergeometric distribution:

Bimax Biclustering Operon Overlap

Source: Prolinks: a database of protein functional linkages derived from coevolution (Bowers et al. 2005)

Random step – lacks reproducibility

No biological soundness

Artificial arrangement of data

◦ Large data sets produce statistically significant, but small clusters

Practicality

◦ Implementation

◦ Large Input Data Sets

K-Means clustering performs better than biclustering on our data set

Next, use motif recognition methods to identify regulatory motifs in clusters

Further development of improved biclustering algorithms

Project TeamRobert Riley (Mentor)Brian Weiner

The Broad InstitueEric LanderCore MembersSRPG Program Members

Summer Research Program in Genomics (SRPG)Shawna YoungBruce BirrenLucia VielmaMaura Silverstein