18 Ekim 2022 Veri seti Açık Erişim

Kuru, Nurdan; Dereli, Onur; Akkoyun, Emrah; Bircan, Aylin; Tastan, Oznur; Adebali, Ogün

Citation Style Language JSON

{
  "DOI": "10.48623/aperta.240636", 
  "abstract": "<p>Evolutionary conservation is a fundamental resource for predicting the substitutability of amino acids and the loss of function in proteins. The use of multiple sequence alignment alone&mdash;without considering the evolutionary relationships among sequences&mdash;results in the redundant counting of evolutionarily related alteration events, as if they were independent. Here, we propose a new method, PHACT, that predicts the pathogenicity of missense mutations directly from the phylogenetic tree of proteins. PHACT travels through the nodes of the phylogenetic tree and evaluates the deleteriousness of a substitution based on the probability differences of ancestral amino acids between neighboring nodes in the tree. Moreover, PHACT assigns weights to each node in the tree based on their distance to the query organism. For each potential amino acid substitution, the algorithm generates a score that is used to calculate the effect of substitution on protein function. To analyze the predictive performance of PHACT, we performed various experiments over the subsets of two datasets that include 3,023 proteins and 61,662 variants in total. The experiments demonstrated that our method outperformed the widely used pathogenicity prediction tools (i.e., SIFT and PolyPhen-2) and achieved a better predictive performance than other conventional statistical approaches presented in dbNSFP. The PHACT source code is available at&nbsp;<a href=\"https://github.com/CompGenomeLab/PHACT\">https://github.com/CompGenomeLab/PHACT</a>.</p>", 
  "author": [
    {
      "family": "Kuru", 
      "given": " Nurdan"
    }, 
    {
      "family": "Dereli", 
      "given": " Onur"
    }, 
    {
      "family": "Akkoyun", 
      "given": " Emrah"
    }, 
    {
      "family": "Bircan", 
      "given": " Aylin"
    }, 
    {
      "family": "Tastan", 
      "given": " Oznur"
    }, 
    {
      "family": "Adebali", 
      "given": " Og\u00fcn"
    }
  ], 
  "container_title": "Molecular Biology and Evolution", 
  "id": "240637", 
  "issue": "6", 
  "issued": {
    "date-parts": [
      [
        2022, 
        10, 
        18
      ]
    ]
  }, 
  "language": "eng", 
  "note": "All data obtained during this study is also shared on the following url. https://phact.sabanciuniv.edu/pubs/kuru_mbe_2022/\nAll the tools,  sw, developed codes is shared on the github page. https://github.com/CompGenomeLab/PHACT\n\nAcknowledgement\nThis work was supported by the Health Institutes of Turkey (TUSEB) (Project no: 4587 to O.A.) and EMBO Installation Grant (Project no: 4163 to O.A.) funded by the Scientific and Technological Research Council of Turkey (T\u00dcB\u0130TAK). Most of the numerical calculations reported in this paper were performed at the High Performance and Grid Computing Center (TRUBA resources) of T\u00dcBITAK. The TOSUN cluster at Sabanci University was also used for computational analyses. We also want to thank Nehircan \u00d6zdemir for his art illustration of the PHACT approach.", 
  "page": "msac114", 
  "title": "[DATASET] PHACT: Phylogeny-Aware Computing of Tolerance for Missense Mutations", 
  "type": "dataset", 
  "version": "v1.0", 
  "volume": "39"
}