Issues in Constructing 3D Chromosome Configurations from Chromatin Conformation Capture Assays

• Activity Number: 165
• Type: Topic Contributed
• Date/Time: Monday, August 5, 2013 : 10:30 AM to 12:20 PM
• Sponsor: Biometrics Section
• Author(s): Mark Segal*+
• Companies: University of California, San Francisco
• Keywords: chromatin conformation ; genome architecture ; constrained optimization ; multi-dimensional scaling ; procrustes fitting ; colocalization

Abstract

The recent development of chromatin conformation capture assays (3C techniques and the related extensions 4C, 5C, Hi-C) has enabled the identification of intra- and inter- chromosomal interactions / contacts on a genomewide scale. As has been demonstrated by several groups, and for several organisms (yeast, drosophila, human), such so-called contact maps can be highly revealing about many aspects of genome organization and function. However, even more informative would be three dimensional (3D) representations of chromosome configurations, if these could be reliably derived from contact maps. Some efforts and algorithms have been advanced along these lines, but very little in the way of assessment in terms of reproducibility, sensitivity (to constraints / algorithm / tuning), accuracy, or generality has been proffered. I describe some of these issues and report results on reproducibility of 3D reconstructions.