Data Fusion by Matrix Factorization

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Abstract

For most problems in science and engineering we can obtain data sets that describe the observed system from various perspectives and record the behavior of its individual components. Heterogeneous data sets can be collectively mined by data fusion. Fusion can focus on a specific target relation and exploit directly associated data together with contextual data and data about system's constraints. In the paper we describe a data fusion approach with penalized matrix tri-factorization (DFMF) that simultaneously factorizes data matrices to reveal hidden associations. The approach can directly consider any data that can be expressed in a matrix, including those from feature-based representations, ontologies, associations and networks. We demonstrate the utility of DFMF for gene function prediction task with eleven different data sources and for prediction of pharmacologic actions by fusing six data sources. Our data fusion algorithm compares favorably to alternative data integration approaches and achieves higher accuracy than can be obtained from any single data source alone.

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The Sequence Alignment/Map format and SAMtools

Heng Li, Bob Handsaker, Alec Wysoker … (2009)

Summary: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. SAMtools implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments. Availability: http://samtools.sourceforge.net Contact: rd@sanger.ac.uk

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Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM

Charles Vaske, Stephen Benz, J Sanborn … (2010)

Motivation: High-throughput data is providing a comprehensive view of the molecular changes in cancer tissues. New technologies allow for the simultaneous genome-wide assay of the state of genome copy number variation, gene expression, DNA methylation and epigenetics of tumor samples and cancer cell lines. Analyses of current data sets find that genetic alterations between patients can differ but often involve common pathways. It is therefore critical to identify relevant pathways involved in cancer progression and detect how they are altered in different patients. Results: We present a novel method for inferring patient-specific genetic activities incorporating curated pathway interactions among genes. A gene is modeled by a factor graph as a set of interconnected variables encoding the expression and known activity of a gene and its products, allowing the incorporation of many types of omic data as evidence. The method predicts the degree to which a pathway's activities (e.g. internal gene states, interactions or high-level ‘outputs’) are altered in the patient using probabilistic inference. Compared with a competing pathway activity inference approach called SPIA, our method identifies altered activities in cancer-related pathways with fewer false-positives in both a glioblastoma multiform (GBM) and a breast cancer dataset. PARADIGM identified consistent pathway-level activities for subsets of the GBM patients that are overlooked when genes are considered in isolation. Further, grouping GBM patients based on their significant pathway perturbations divides them into clinically-relevant subgroups having significantly different survival outcomes. These findings suggest that therapeutics might be chosen that target genes at critical points in the commonly perturbed pathway(s) of a group of patients. Availability:Source code available at http://sbenz.github.com/Paradigm Contact: jstuart@soe.ucsc.edu Supplementary information: Supplementary data are available at Bioinformatics online.

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Gene prioritization through genomic data fusion.

Stein Aerts, Diether Lambrechts, Sunit Maity … (2006)

The identification of genes involved in health and disease remains a challenge. We describe a bioinformatics approach, together with a freely accessible, interactive and flexible software termed Endeavour, to prioritize candidate genes underlying biological processes or diseases, based on their similarity to known genes involved in these phenomena. Unlike previous approaches, ours generates distinct prioritizations for multiple heterogeneous data sources, which are then integrated, or fused, into a global ranking using order statistics. In addition, it offers the flexibility of including additional data sources. Validation of our approach revealed it was able to efficiently prioritize 627 genes in disease data sets and 76 genes in biological pathway sets, identify candidates of 16 mono- or polygenic diseases, and discover regulatory genes of myeloid differentiation. Furthermore, the approach identified a novel gene involved in craniofacial development from a 2-Mb chromosomal region, deleted in some patients with DiGeorge-like birth defects. The approach described here offers an alternative integrative method for gene discovery.