The replication of human genome proceeds in a defined temporal sequence (“replication timing program”) that can be altered by many temporary or permanent states in the organism such as epigenetic modifications, diseases and cell differentiation. Replication timing is regulated during development and replication correlates strongly with transcription, chromatin conformation, nuclear lamina binding and histone modifications. Thus studies of replication timing provide insight into poorly understood aspects of large-scale chromosome architecture and their significance to cell development and functionality. Despite these compelling structure-function correlations, causal linkages between DNA modification, DNA replication, chromatin architecture and transcription still remain obscure.
This workshop, in conjunction with ACM BCB 2013, aims to explore the relationship between epigenetic modifications, DNA replication, interactions among molecules and cell functions. The workshop will bring in researchers from epigenomics, proteomics, regulatory genomics and systems biology to discuss the most recent results in the field. The workshop will particularly focus on the key computational challenges and new algorithmic developments that establish the causality among emerging epigenomics datasets. Example topics will include (but it is not limited to):
- Identifying the causality between epigenetic modifications, DNA replication, transcription and gene regulation
- Novel methods for predicting the impacts of the gene loci on DNA replication/modification
- Tackling the scalability issues regarding mining massive epigenomic and DNA replication data
- Computational models of chromatin structure
- Methods for integrating heterogeneous epigenomic data such as nucleosome positioning, DNA methylation and acetlyation
- Methods for predicting gene expression changes using epigenomic data
Molecular & Computational Biology, Department of Biological Sciences
University of Southern California
Frank Alber received his Ph.D. training at the Swiss Federal Institute of Technology (ETH) in Zurich and carried out postdoctoral research at the Rockefeller University and at the University of California San Francisco (UCSF). His lab focuses on computational approaches for the comprehensive integration of varied experimental data to study the 3D spatial organization of genome architectures and their role in functional processes, such as transcription and replication. In addition his lab studies the spatial organization of the cellular proteome, by large-scale detection of macromolecular assemblies in crowded cellular environments using image analysis technologies. He joined the faculty of the University of Southern California (USC) in 2008 and is currently an Associate Professor in the Molecular and Computational Biology section. He was awarded with an Alfred P. Sloan research fellowship (2009), a PEW scholarship in the biomedical sciences (2009), a NSF career award (2012), and a Beckman Young investigator award (2012).
Talk Title: Exploring the 3D spatial organization of genomes
Knowledge about the 3-D organization of the genome will offer great insights into how cells retrieve and process the genetic information. Knowing the spatial probability distributions of individual genes may provide insights into gene regulatory and replication processes, and fill in the missing links between epigenomics, functional genomics and structural biology. We will discuss an approach to determine 3D genome structures and structure-function maps of genomes by integrating divers types of data. To address the challenge of modeling highly variable genome structures, we discuss a population based modeling approach, where we construct a large population of 3D genome structures that together are entirely consistent with all available experimental data including data from genome-wide chromosome-conformation capture and imaging experiments. We interpret the result in terms of probabilities of a sample drawn from a population of heterogeneous structures. We will discuss results on the 3D spatial organization of genomes in human cells and budding yeast.