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1.  Atlas2 Cloud: a framework for personal genome analysis in the cloud 
BMC Genomics  2012;13(Suppl 6):S19.
Until recently, sequencing has primarily been carried out in large genome centers which have invested heavily in developing the computational infrastructure that enables genomic sequence analysis. The recent advancements in next generation sequencing (NGS) have led to a wide dissemination of sequencing technologies and data, to highly diverse research groups. It is expected that clinical sequencing will become part of diagnostic routines shortly. However, limited accessibility to computational infrastructure and high quality bioinformatic tools, and the demand for personnel skilled in data analysis and interpretation remains a serious bottleneck. To this end, the cloud computing and Software-as-a-Service (SaaS) technologies can help address these issues.
We successfully enabled the Atlas2 Cloud pipeline for personal genome analysis on two different cloud service platforms: a community cloud via the Genboree Workbench, and a commercial cloud via the Amazon Web Services using Software-as-a-Service model. We report a case study of personal genome analysis using our Atlas2 Genboree pipeline. We also outline a detailed cost structure for running Atlas2 Amazon on whole exome capture data, providing cost projections in terms of storage, compute and I/O when running Atlas2 Amazon on a large data set.
We find that providing a web interface and an optimized pipeline clearly facilitates usage of cloud computing for personal genome analysis, but for it to be routinely used for large scale projects there needs to be a paradigm shift in the way we develop tools, in standard operating procedures, and in funding mechanisms.
PMCID: PMC3481437  PMID: 23134663
2.  The PHD and Chromo Domains Regulate the ATPase Activity of the Human Chromatin Remodeler CHD4 
Journal of Molecular Biology  2012;422(1-2):3-17.
The NuRD (nucleosome remodeling and deacetylase) complex serves as a crucial epigenetic regulator of cell differentiation, proliferation, and hematopoietic development by coupling the deacetylation and demethylation of histones, nucleosome mobilization, and the recruitment of transcription factors. The core nucleosome remodeling function of the mammalian NuRD complex is executed by the helicase-domain-containing ATPase CHD4 (Mi-2β) subunit, which also contains N-terminal plant homeodomain (PHD) and chromo domains. The mode of regulation of chromatin remodeling by CHD4 is not well understood, nor is the role of its PHD and chromo domains. Here, we use small-angle X-ray scattering, nucleosome binding ATPase and remodeling assays, limited proteolysis, cross-linking, and tandem mass spectrometry to propose a three-dimensional structural model describing the overall shape and domain interactions of CHD4 and discuss the relevance of these for regulating the remodeling of chromatin by the NuRD complex.
Graphical Abstract
► The ATPase CHD4 mediates nucleosome remodeling by the NuRD complex. ► We present a three-dimensional small-angle X-ray scattering model of CHD4 and define its interdomain interactions. ► Cross-linking and limited proteolysis studies validate our model. ► Functional and binding assays suggest a regulatory role for the PHD and chromo domains.
PMCID: PMC3437443  PMID: 22575888
CHD, chromo domain helicase DNA binding; NuRD, nucleosome remodeling and deacetylase; PHD, plant homeodomain; SAXS, small-angle X-ray scattering; LC–MS/MS, liquid chromatography–tandem mass spectrometry; DUF, domain of unknown function; TEV, tobacco etch virus; HRP, horseradish peroxidase; BSA, bovine serum albumin; Bistris, 2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol; NuRD complex; chromatin remodeling; chromo domain helicase DNA-binding protein 4; histone; transcriptional regulation

Results 1-2 (2)