title: Analysis of interactions between the epigenome and structural mutability of the genome using Genboree Workbench tools.
abstract: BACKGROUND
  Interactions between the epigenome and structural genomic variation are potentially bi-directional. In one direction, structural variants may cause epigenomic changes in cis. In the other direction, specific local epigenomic states such as DNA hypomethylation associate with local genomic instability.
  
  
  METHODS
  To study these interactions, we have developed several tools and exposed them to the scientific community using the Software-as-a-Service model via the Genboree Workbench. One key tool is Breakout, an algorithm for fast and accurate detection of structural variants from mate pair sequencing data.
  
  
  RESULTS
  By applying Breakout and other Genboree Workbench tools we map breakpoints in breast and prostate cancer cell lines and tumors, discriminate between polymorphic breakpoints of germline origin and those of somatic origin, and analyze both types of breakpoints in the context of the Human Epigenome Atlas, ENCODE databases, and other sources of epigenomic profiles. We confirm previous findings that genomic instability in human germline associates with hypomethylation of DNA, binding sites of Suz12, a key member of the PRC2 Polycomb complex, and with PRC2-associated histone marks H3K27me3 and H3K9me3. Breakpoints in germline and in breast cancer associate with distal regulatory of active gene transcription. Breast cancer cell lines and tumors show distinct patterns of structural mutability depending on their ER, PR, or HER2 status.
  
  
  CONCLUSIONS
  The patterns of association that we detected suggest that cell-type specific epigenomes may determine cell-type specific patterns of selective structural mutability of the genome.
authors: Cristian
authors: C
authors: Coarfa
authors: Christina
authors: C
authors: Pichot
authors: Andrew
authors: A
authors: Jackson
authors: Arpit
authors: A
authors: Tandon
authors: Viren
authors: V
authors: Amin
authors: Sriram
authors: S
authors: Raghuraman
authors: Sameer
authors: S
authors: Paithankar
authors: Adrian V
authors: AV
authors: Lee
authors: Sean E
authors: SE
authors: McGuire
authors: Aleksandar
authors: A
authors: Milosavljevic
mesh_terms: D000465:Algorithms; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods*; D015894:Genome, Human; D042822:Genomic Instability; D005854:Germ Cells / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D012984:Software
chemical_list: D006657:Histones; D004247:DNA