We are analyzing https://link.springer.com/article/10.1186/s12859-020-03759-0.

Title:
Protein–protein and protein-nucleic acid binding residues important for common and rare sequence variants in human | BMC Bioinformatics
Description:
Background Any two unrelated people differ by about 20,000 missense mutations (also referred to as SAVs: Single Amino acid Variants or missense SNV). Many SAVs have been predicted to strongly affect molecular protein function. Common SAVs (> 5% of population) were predicted to have, on average, more effect on molecular protein function than rare SAVs (< 1% of population). We hypothesized that the prevalence of effect in common over rare SAVs might partially be caused by common SAVs more often occurring at interfaces of proteins with other proteins, DNA, or RNA, thereby creating subgroup-specific phenotypes. We analyzed SAVs from 60,706 people through the lens of two prediction methods, one (SNAP2) predicting the effects of SAVs on molecular protein function, the other (ProNA2020) predicting residues in DNA-, RNA- and protein-binding interfaces. Results Three results stood out. Firstly, SAVs predicted to occur at binding interfaces were predicted to more likely affect molecular function than those predicted as not binding (p value < 2.2 × 10–16). Secondly, for SAVs predicted to occur at binding interfaces, common SAVs were predicted more strongly with effect on protein function than rare SAVs (p value < 2.2 × 10–16). Restriction to SAVs with experimental annotations confirmed all results, although the resulting subsets were too small to establish statistical significance for any result. Thirdly, the fraction of SAVs predicted at binding interfaces differed significantly between tissues, e.g. urinary bladder tissue was found abundant in SAVs predicted at protein-binding interfaces, and reproductive tissues (ovary, testis, vagina, seminal vesicle and endometrium) in SAVs predicted at DNA-binding interfaces. Conclusions Overall, the results suggested that residues at protein-, DNA-, and RNA-binding interfaces contributed toward predicting that common SAVs more likely affect molecular function than rare SAVs.
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Keywords {🔍}

savs, predicted, binding, common, protein, rare, effect, residues, pubmed, pronabinding, article, fig, function, interfaces, google, scholar, cas, additional, variants, file, molecular, table, proteins, dna, prona, experimental, annotations, data, predictions, observed, prediction, rna, central, snap, results, snapscores, human, higher, interface, sequence, amino, analysis, acid, rost, snapscore, nonbinding, strongly, affect, structure, single,

Topics {✒️}

protein-coding genetic variation macro-molecular binding interfaces braf-mek complex reveals false positives/false negatives de beer tap macro-molecule binding interfaces savs/missense snvs/missense mutations full size image deep mutational scanning disease-related mutations predicted uniprotkb/swiss-prot sequence [35] amino acid variants amino acid sequence article download pdf protein–protein interaction protein-protein interaction creating subgroup-specific phenotypes cancer genes affect protein-protein binding proteins prona-binding interfaces differed prona-binding interface increased prona-binding interface residues related subjects rna-binding interfaces contributed predicts disease-affecting savs hopf ta sequence-based predictions protein structure prediction high-resolution 3d structures high-resolution 3d information amino acid “native” common versus rare machine-learning-based part prona-binding positions predicted protein structure stability predicted prona-binding interfaces full access prona2020 predicts protein-dna experimental 3d structure affect molecular function prona-binding residues experimentally protein function exist molecular protein function random background predictions magenta-colored dots privacy choices/manage cookies prona-binding interfaces explained query protein close molecular protein functions high-resolution experiments

Questions {❓}

Common sequence variants affect molecular function more than rare variants?
Common sequence variants affect molecular function more than rare variants?

Schema {🗺️}

WebPage:
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         headline:Protein–protein and protein-nucleic acid binding residues important for common and rare sequence variants in human
         description:Any two unrelated people differ by about 20,000 missense mutations (also referred to as SAVs: Single Amino acid Variants or missense SNV). Many SAVs have been predicted to strongly affect molecular protein function. Common SAVs (> 5% of population) were predicted to have, on average, more effect on molecular protein function than rare SAVs (< 1% of population). We hypothesized that the prevalence of effect in common over rare SAVs might partially be caused by common SAVs more often occurring at interfaces of proteins with other proteins, DNA, or RNA, thereby creating subgroup-specific phenotypes. We analyzed SAVs from 60,706 people through the lens of two prediction methods, one (SNAP2) predicting the effects of SAVs on molecular protein function, the other (ProNA2020) predicting residues in DNA-, RNA- and protein-binding interfaces. Three results stood out. Firstly, SAVs predicted to occur at binding interfaces were predicted to more likely affect molecular function than those predicted as not binding (p value < 2.2 × 10–16). Secondly, for SAVs predicted to occur at binding interfaces, common SAVs were predicted more strongly with effect on protein function than rare SAVs (p value < 2.2 × 10–16). Restriction to SAVs with experimental annotations confirmed all results, although the resulting subsets were too small to establish statistical significance for any result. Thirdly, the fraction of SAVs predicted at binding interfaces differed significantly between tissues, e.g. urinary bladder tissue was found abundant in SAVs predicted at protein-binding interfaces, and reproductive tissues (ovary, testis, vagina, seminal vesicle and endometrium) in SAVs predicted at DNA-binding interfaces. Overall, the results suggested that residues at protein-, DNA-, and RNA-binding interfaces contributed toward predicting that common SAVs more likely affect molecular function than rare SAVs.
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            Genome sequence analysis
            Single amino acid variants (SAVs)
            Macro-molecular binding residues
            DNA-binding
            RNA-binding
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            Common versus rare sequence variants
            Effect of sequence diversity
            Bioinformatics
            Microarrays
            Computational Biology/Bioinformatics
            Computer Appl. in Life Sciences
            Algorithms
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      headline:Protein–protein and protein-nucleic acid binding residues important for common and rare sequence variants in human
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         Genome sequence analysis
         Single amino acid variants (SAVs)
         Macro-molecular binding residues
         DNA-binding
         RNA-binding
         Protein–protein binding
         Common versus rare sequence variants
         Effect of sequence diversity
         Bioinformatics
         Microarrays
         Computational Biology/Bioinformatics
         Computer Appl. in Life Sciences
         Algorithms
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      name:TUM Graduate School, Center of Doctoral Studies in Informatics and Its Applications (CeDoSIA), Garching, Germany
      name:Biobank of Ninth People’s Hospital, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
      name:Department of Informatics, I12-Chair of Bioinformatics and Computational Biology, Technical University of Munich (TUM), Garching, Munich, Germany
      name:TUM Graduate School, Center of Doctoral Studies in Informatics and Its Applications (CeDoSIA), Garching, Germany
      name:Department of Informatics, I12-Chair of Bioinformatics and Computational Biology, Technical University of Munich (TUM), Garching, Munich, Germany
      name:Institute of Advanced Study (TUM-IAS), Garching, Munich, Germany
      name:Institute for Food and Plant Sciences (WZW) Weihenstephan, Freising, Germany

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