Massively parallel sequencing technology and the associated rapidly decreasing sequencing costs have enabled systemic analyses of somatic mutations in large cohorts of cancer cases. Here we introduce a comprehensive mutational analysis pipeline that uses standardized sequence-based inputs along with multiple types of clinical data to establish correlations among mutation sites, affected genes and pathways, and to ultimately separate the commonly abundant passenger mutations from the truly significant events. In other words, we aim to determine the Mutational Significance in Cancer (MuSiC) for these large data sets. The integration of analytical operations in the MuSiC framework is widely applicable to a broad set of tumor types and offers the benefits of automation as well as standardization. Herein, we describe the computational structure and statistical underpinnings of the MuSiC pipeline and demonstrate its performance using 316 ovarian cancer samples from the TCGA ovarian cancer project. MuSiC correctly confirms many expected results, and identifies several potentially novel avenues for discovery.

The Drug-Gene Interaction database (DGIdb) mines existing resources that generate hypotheses about how mutated genes might be targeted therapeutically or prioritized for drug development. It provides an interface for searching lists of genes against a compendium of drug-gene interactions and potentially druggable genes. DGIdb can be accessed at dgidb.org.

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms.

Emission in the H I 21 cm line has been mapped for a region of the Galaxy that includes two known supershells, GS 018 [04] 44 and GS 034[06]65. We focus on the GS 018 [04]44, hereafter referred to as the Scutum Supershell, which is an elongated shell about 5¡ in diameter extending to [7¡ below the Galactic plane. The Scutum shell lies at a kinematic distance of D3300 pc, implying a shell diameter of D290 pc with a vertical extension of D400 pc away from the Galactic plane. The Scutum shell contains 6.2 ] 105 swept into the walls. We observe that the top of the shell is missing, and a substan-M _ tial column of H I rises from the shell walls to b \ [11¡, culminating in a large cloud of neutral hydrogen, 3.74 ] 104 located D630 pc from the plane. ROSAT data show X-ray emission that M _ , closely anticorrelates with the 21 cm emission. This emission probably originates from hot gas within the Scutum Supershell. After approximately correcting for the foreground absorption, we Ðnd that the 1.5 keV X-rays peak at the base of the shell, the 0.75 keV emission peaks in the interior and at the top of the shell, and the 0.25 keV emission extends to high latitudes above the shell. The X-ray luminosity is roughly D5 ] 1036 ergs s~1. The Wisconsin H-Alpha Mapper (WHAM) survey shows the presence of Ha emission that exhibits a morphology similar to that of the H I. Spectra indicate the presence of ionized hydrogen at velocities similar to the H I, placing ionized material at the same kinematic distance as the neutral material. IRAS images in the 60 and 100 km wavebands reveal the presence of dust correlated with the neutral hydrogen. Infrared surface brightness indicates an excess in the 100 km emission, which could indicate a molecular hydrogen component with a column density of 2.4 ] 1021 cm~2 in the densest regions of the high-latitude cloud of neutral hydrogen. IUE ultraviolet high dispersion spectra of HD 177989and HD 175754 reveal the presence of very92) strong absorption by highly ionized gas at a velocity that associates the absorption with the ejecta of the Scutum Supershell. In the case of HD 177989, the high ion column density ratios suggest an origin in a turbulent mixing layer where hot and cool gases mix in the presence of shear Ñows. The Ha and X-ray emission suggest that a multitude of energetic phenomena exist in this region, providing the necessary ionizing radiation. Indeed, there are multiple supernova remnants, H II regions, and hot stars, which could all contribute sizeable amounts of energy and ionizing radiation. The combination of these data sets indicates observational evidence of a "" blowout ÏÏ phenomena whereby hot material produced within the Scutum Supershell has blown through the top of the shell and been pushed to high latitude.