This study was supported by Wellcome Trust [grant number WT101477MA] (http://www.wellcome.ac.uk/), BBSRC [grant numbers BB/K01997X/1, BB/I00095X/1, BB/L024225/1 and BB/L002817/1] (http://www.bbsrc.ac.uk/), BMBF grant de.NBI - German Network for Bioinformatics Infrastructure (FKZ031 A 534A) (https://www.denbi.de/), NIH grant numbers R01-GM-094231 and R01-EB-017205 (http://www.nih.gov/), EPSRC [reference EP/M022641/1] (https://www.epsrc.ac.uk), NSF grant number 1252893 (http://www.nsf.gov/), and Novo Nordisk Foundation (http://www.novonordiskfonden.dk/en).A 'Ten Simple Rules' guide to Git and GitHub. We describe and provide examples on how to use these software to track projects, as users, teams and organizations. We document collaborative development using branching and forking, interaction between collaborators using issues and continuous integration and automation using, for example, Travis CI and codevoc. We also describe dissemination and social aspects of GitHub such as GitHub pages, following and watching repositories, and give advice on how to make code citable.Publisher PDFPeer reviewe
Poly (ADP-ribose) polymerase-1 (PARP1) is a nuclear enzyme involved in DNA repair, chromatin remodeling and gene expression. PARP1 interactions with chromatin architectural multi-protein complexes (i.e. nucleosomes) alter chromatin structure resulting in changes in gene expression. Chromatin structure impacts gene regulatory processes including transcription, splicing, DNA repair, replication and recombination. It is important to delineate whether PARP1 randomly associates with nucleosomes or is present at specific nucleosome regions throughout the cell genome. We performed genome-wide association studies in breast cancer cell lines to address these questions. Our studies show that PARP1 associates with epigenetic regulatory elements genome-wide, such as active histone marks, CTCF and DNase hypersensitive sites. Additionally, the binding of PARP1 to chromatin genome-wide is mutually exclusive with DNA methylation pattern suggesting a functional interplay between PARP1 and DNA methylation. Indeed, inhibition of PARylation results in genome-wide changes in DNA methylation patterns. Our results suggest that PARP1 controls the fidelity of gene transcription and marks actively transcribed gene regions by selectively binding to transcriptionally active chromatin. These studies provide a platform for developing our understanding of PARP1’s role in gene regulation.
New metabolomics applications of ultra-high resolution and accuracy mass spectrometry can provide thousands of detectable isotopologues, with the number of potentially detectable isotopologues increasing exponentially with the number of stable isotopes used in newer isotope tracing methods like stable isotope-resolved metabolomics (SIRM) experiments. This huge increase in usable data requires software capable of correcting the large number of isotopologue peaks resulting from SIRM experiments in a timely manner. We describe the design of a new algorithm and software system capable of handling these high volumes of data, while including quality control methods for maintaining data quality. We validate this new algorithm against a previous single isotope correction algorithm in a two-step cross-validation. Next, we demonstrate the algorithm and correct for the effects of natural abundance for both 13C and 15N isotopes on a set of raw isotopologue intensities of UDP-N-acetyl-D-glucosamine derived from a 13C/15N-tracing experiment. Finally, we demonstrate the algorithm on a full omics-level dataset.