luke alden yancy, jr. mentor: robert riley broad institute of mit & harvard cambridge, ma
TRANSCRIPT
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