Computational Modeling and Analysis of Chromatin Structure
Author | : Mathieu Rousseau |
Publisher | : |
Total Pages | : |
Release | : 2013 |
ISBN-10 | : OCLC:922007843 |
ISBN-13 | : |
Rating | : 4/5 (43 Downloads) |
Book excerpt: "The organization of DNA in the nucleus of a cell has long been known to play an important role in processes such as DNA replication and repair, and the regulation of gene expression. Recent advances in microarray and high-throughput sequencing technologies have enabled the creation of novel techniques for measuring certain aspects of the three-dimensional conformation of chromatin in vivo. The data generated by these methods contain both structural information and noise from the experimental procedures. Methods for modeling and analyzing these data to infer three-dimensional chromatin structure will constitute invaluable tools in the discovery of the mechanism by which chromatin structure is mediated. The overall objective of my thesis is to develop robust three-dimensional computational models of DNA and to analyze these data to gain biological insight into the role of chromatin structure on cellular processes. This thesis presents three main results, firstly, a novel computational modeling and analysis approach for the inference of three-dimensional structure from chromatin conformation capture carbon copy (5C) and Hi-C data. Our method named MCMC5C is based on Markov chain Monte Carlo sampling and can generate representative ensembles of three-dimensional models from noisy experimental data. Secondly, our investigation of the relationship between chromatin structure and gene expression during cellular differentiation shows that chromatin architecture is a dynamic structure which adopts an open conformation for actively transcribed genes and a condensed conformation for repressed genes. And thirdly, we developed a support vector machine classifier from 5C data and demonstrate a proof-of-concept that chromatin conformation signatures could be used to discriminate between human acute lymphoid and myeloid leukemias." --