Mapping the proteo-genomic convergence of human diseases

Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3892 plasma proteins to create a cis-anchored gene-protein-disease map of 1859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to connect etiologically related diseases, to provide biological context for new or emerging disorders, and to integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at loci identified in genome-wide association studies, thereby addressing a major barrier to experimental validation and clinical translation of genetic discoveries

Managing and Sharing the Escalating Number of Sponge "Unknowns": The SpongeMaps Project

Contemporary collections of sponges in the Indo-west Pacific have escalated substantially due to pharmaceutical discovery, national bioregional planning, and compliance with international conventions on the seabed and its marine genetic resources beyond national jurisdictions. These partially processed operational taxonomic unit (OTU) collections now vastly outweigh the expertise available to make them better "known" via complete taxonomy, yet for many bioregions they represent the most significant body of currently available knowledge. Increasing numbers of cryptic species, previously undetected morphologically, are now being discovered by molecular and chemical analyses. The uncoordinated and fragmented nature of many previous collections, however, means that knowledge and expertise gained from a particular project are often lost to future projects without a biodiversity informatics legacy. Integrating these diverse data (GIS; OTUs; images; molecular, chemical, and other datasets) required a two-way iterative process so far unavailable for sponges with existing biodiversity informatics tools. SpongeMaps arose from the initial need for online collaboration to integrate morphometric data with molecular barcodes, including the Porifera Tree of Life (PorTol) project. It provides interrogation of existing data to better process new collections; capacity to create new OTUs; publication of online pages for individual species, so as to interpret GIS and other data for online biodiversity databases and services; and automatic links to external datasets for taxonomic hierarchy, specimen GIS and mapping, DNA sequence data, chemical structures, and images

Allele-specific methylation of type 1 diabetes susceptibility genes

The susceptibility to autoimmune diseases is influenced by genes encoding major histocompatibility complex (MHC) proteins. By examining the epigenetic methylation maps of cord blood samples, we found marked differences in the methylation status of CpG sites within the MHC genes (cis-metQTLs) between carriers of the type 1 diabetes risk haplotypes HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) and HLA-DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8). These differences were found in children and adults, and were accompanied by reduced HLA-DR protein expression in immune cells with the HLA-DR3-DQ2 haplotype. Extensive cis-metQTLs were identified in all 45 immune and non-immune type 1 diabetes susceptibility genes analyzed in this study. We observed and validated a novel association between the methylation status of CpG sites within the LDHC gene and the development of insulin autoantibodies in early childhood in children who are carriers of the highest type 1 diabetes risk genotype. Functionally relevant epigenetic changes in susceptibility genes may represent therapeutic targets for type 1 diabetes