13 research outputs found

    A Network-Based Approach to Prioritize Results from Genome-Wide Association Studies

    Get PDF
    Genome-wide association studies (GWAS) are a valuable approach to understanding the genetic basis of complex traits. One of the challenges of GWAS is the translation of genetic association results into biological hypotheses suitable for further investigation in the laboratory. To address this challenge, we introduce Network Interface Miner for Multigenic Interactions (NIMMI), a network-based method that combines GWAS data with human protein-protein interaction data (PPI). NIMMI builds biological networks weighted by connectivity, which is estimated by use of a modification of the Google PageRank algorithm. These weights are then combined with genetic association p-values derived from GWAS, producing what we call ‘trait prioritized sub-networks.’ As a proof of principle, NIMMI was tested on three GWAS datasets previously analyzed for height, a classical polygenic trait. Despite differences in sample size and ancestry, NIMMI captured 95% of the known height associated genes within the top 20% of ranked sub-networks, far better than what could be achieved by a single-locus approach. The top 2% of NIMMI height-prioritized sub-networks were significantly enriched for genes involved in transcription, signal transduction, transport, and gene expression, as well as nucleic acid, phosphate, protein, and zinc metabolism. All of these sub-networks were ranked near the top across all three height GWAS datasets we tested. We also tested NIMMI on a categorical phenotype, Crohn’s disease. NIMMI prioritized sub-networks involved in B- and T-cell receptor, chemokine, interleukin, and other pathways consistent with the known autoimmune nature of Crohn’s disease. NIMMI is a simple, user-friendly, open-source software tool that efficiently combines genetic association data with biological networks, translating GWAS findings into biological hypotheses

    Fourier-transform infrared photopyroelectric spectroscopy of solids: a new technique

    No full text
    A novel anal. technique, Fourier-transform IR photopyroelec. spectroscopy (FT-IR-P2ES) is demonstrated and applied to spectroscopic investigations of solid materials. The salient features of the technique and its advantages over other conventional FT-IR photothermal methods are discussed. A few selected quant. applications are presented as examples of the versatility and sensitivity of the new technique

    La predissociation rotationnelle des ions CH4+ et CD4+.

    Full text link
    The metastable transitions producing CH3+/CH4 and CD3+/CD4 have been investigated by means of translational spectroscopy. For the first time structures are observed in a metastable peak corresponding to the dissociation of a polyatomic ion. They are interpreted by tunneling through a rotational barrier from discrete quasi-bound states. Kinetic energy releases have been measured
    corecore