Network-based elucidation of human disease similarity reveals common functional modules enriched for pluripotent drug targets.

Current work in elucidating relationships between diseases has largely been based on pre-existing knowledge of disease genes. Consequently, these studies are limited in their discovery of new and unknown disease relationships. We present the first quantitative framework to compare and contrast diseases by an integrated analysis of disease-related mRNA expression data and the human protein interaction network. We identified 4,620 functional...

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Validation of Hepascore, compared to simple indices of fibrosis, in US patients with chronic hepatitis C virus infection.

BACKGROUND & AIMS: Biomarkers are being developed as alternatives to liver biopsy for predicting liver fibrosis in patients with chronic hepatitis C. Hepascore uses noninvasive serum markers and has been validated in Australian and European populations for predicting different degrees of fibrosis. This study validated this test in a U.S. population. METHODS: Patients with chronic hepatitis C virus infection were assigned to training (n =...

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Similarly strong purifying selection acts on human disease genes of all evolutionary ages.

A number of studies have showed that recently created genes differ from the genes created in deep evolutionary past in many aspects. Here, we determined the age of emergence and propensity for gene loss (PGL) of all human protein-coding genes and compared disease genes with non-disease genes in terms of their evolutionary rate, strength of purifying selection, mRNA expression, and genetic redundancy. The older and the less prone to loss,...

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Identifying compartment-specific alloimmune targets after renal transplantation by integrating transcriptome and antibodyome measures.

Microarray technology has evolved as a powerful tool over the last decade, to identify biomarkers and study the mechanisms of diseases. We propose a novel application of integrated genomics by combining transcriptional levels with serological antibody profiling after kidney transplantation, with the aim of uncovering the relative immunogenicity of seven different renal compartments after allo-transplantation. Thirty-six paired pre- and...

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Ontology-driven indexing of public datasets for translational bioinformatics.

The volume of publicly available genomic scale data is increasing. Genomic datasets in public repositories are annotated with free-text fields describing the pathological state of the studied sample. These annotations are not mapped to concepts in any ontology, making it difficult to integrate these datasets across repositories. We have previously developed methods to map text-annotations of tissue microarrays to concepts in the NCI thesaurus...

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