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Large-scale plasma proteomics comparisons through genetics and disease associations

High-throughput proteomics platforms measuring thousands of proteins in plasma combined with genomic and phenotypic information have the power to bridge the gap between the genome and diseases. Here we performed association studies of Olink Explore 3072 data generated by the UK Biobank Pharma Proteomics Project1 on plasma samples from more than 50,000 UK Biobank participants with phenotypic and genotypic data, stratifying on British or Irish, African and South Asian ancestries. We compared the results with those of a SomaScan v4 study on plasma from 36,000 Icelandic people2, for 1,514 of whom Olink data were also available. We found modest correlation between the two platforms. Although cis protein quantitative trait loci were detected for a similar absolute number of assays on the two platforms (2,101 on Olink versus 2,120 on SomaScan), the proportion of assays with such supporting evidence for assay performance was higher on the Olink platform (72% versus 43%). A considerable number ....

South Korea , Alzheimers Dement , Le Loupp , Uniprot Consortium , Genomes Project Consortium , United Kingdom , Cell Sci , Arthritis Rheum , Acids Res , United Kingdom Biobank , Olink Proteomics , Nucleic Acids , File Specification Technical Note , Methods Primers ,

The status of the human gene catalogue

Scientists have been trying to identify every gene in the human genome since the initial draft was published in 2001. In the years since, much progress has been made in identifying protein-coding genes, currently estimated to number fewer than 20,000, with an ever-expanding number of distinct protein-coding isoforms. Here we review the status of the human gene catalogue and the efforts to complete it in recent years. Beside the ongoing annotation of protein-coding genes, their isoforms and pseudogenes, the invention of high-throughput RNA sequencing and other technological breakthroughs have led to a rapid growth in the number of reported non-coding RNA genes. For most of these non-coding RNAs, the functional relevance is currently unclear; we look at recent advances that offer paths forward to identifying their functions and towards eventually completing the human gene catalogue. Finally, we examine the need for a universal annotation standard that includes all medically significant g ....

Puerto Rico , United States , Puerto Rican , Human Services , Encode Project Consortium , Rnacentral Consortium , Gtex Consortium , Us Department Of Health , Us Department Of Energy , International Human Genome Sequencing Consortium , Uniprot Consortium , Genetic Inheritance , Genome Project , First Five Years , Encode Project , Acids Res , Human Genome Sequencing , Genome Biol , Cell Biol , Ensembl Variant Effect Predictor A , Southern Han Chinese , Nucleic Acids Res ,

Frontiers | Crystal structures of glycoprotein D of equine alphaherpesviruses reveal potential binding sites to the entry receptor MHC-I

Cell entry of most alphaherpesviruses is mediated by the binding of glycoprotein D (gD) to different cell surface receptors. Equine herpesvirus type 1 (EHV-1) and EHV-4 gDs interact with equine major histocompatibility complex I (MHC-I) to initiate entry into equine cells. We have characterized the gD-MHC-I interaction by solving the crystal structures of EHV-1 and EHV-4 gDs (gD1, gD4), performing protein-protein docking simulations, surface plasmon resonance (SPR) analysis, and biological assays. The structures of gD1 and gD4 revealed the existence of a common V-set immunoglobulin-like (IgV-like) core comparable to those of other gD homologs. Molecular modeling yielded plausible binding hypotheses and identified key residues (F213 and D261) that are important for virus binding. Altering the key residues resulted in impaired virus growth in cells, which highlights the important role of these residues in the gD-MHC-I interaction. Taken together, our results add to our understanding of t ....

Mecklenburg Vorpommern , United States , New York , Uppsala Lan , United Kingdom , Baden Wüberg , New Zealand General , New Zealand , San Diego , Richmond Upon Thames , City Of , Nordrhein Westfalen , Deutsche Forschungsgemeinschaft , Applichem Gm , Cytexpert Beckman Coulter , Los Alamos , Clustalomega Sievers , Eva Crosas , Biochom Gm , Santa Barbara , Bruker Daltonics , Santa Clara , Zeiss Axiovert , Molekulare Pharmakologie , David Machalz , Molprobity Williams ,

Small Molecule Drug Discovery Can AI Do It All

The hope is that AI can solve the single most challenging problem at the heart of modern drug discovery: the reliable prediction of novel small. ....

Deepmind Alphafold , Anirban Datta , Protein Data Bank Archive , Verseon International Corporation , Burger King , Tesla Motors , Merck Kga , Uniprot Consortium , Merck Kgaa , Recursion Pharmaceuticals , Verseon International , Insilico Medicine , Generate Biomedicines , The Availability Of Copious Relevant Training , Vastly Different And Much Bigger , Big Pharma , Deep Learning Is Hitting , Protein Data Bank , Methods Mol ,