SuperDCA for genome-wide epistasis analysis

Santeri Puranen, Maiju Pesonen, Johan Pensar, Yingying Xu, John A. Lees, Stephen Bentley, Nicholas J Croucher, Jukka Corander

Tutkimustuotos: LehtiartikkeliArticleScientificvertaisarvioitu

7 Sitaatiot (Scopus)
20 Lataukset (Pure)

Abstrakti

The potential for genome-wide modelling of epistasis has recently surfaced given the possibility of sequencing densely sampled populations and the emerging families of statistical interaction models. Direct coupling analysis (DCA) has previously been shown to yield valuable predictions for single protein structures, and has recently been extended to genome-wide analysis of bacteria, identifying novel interactions in the co-evolution between resistance, virulence and core genome elements. However, earlier computational DCA methods have not been scalable to enable model fitting simultaneously to 104–105 polymorphisms, representing the amount of core genomic variation observed in analyses of many bacterial species. Here, we introduce a novel inference method (SuperDCA) that employs a new scoring principle, efficient parallelization, optimization and filtering on phylogenetic information to achieve scalability for up to 105 polymorphisms. Using two large population samples of Streptococcus pneumoniae, we demonstrate the ability of SuperDCA to make additional significant biological findings about this major human pathogen. We also show that our method can uncover signals of selection that are not detectable by genome-wide association analysis, even though our analysis does not require phenotypic measurements. SuperDCA, thus, holds considerable potential in building understanding about numerous organisms at a systems biological level.
AlkuperäiskieliEnglanti
JulkaisuMicrobial Genomics
Vuosikerta4
Numero6
DOI - pysyväislinkit
TilaJulkaistu - 29 toukokuuta 2018
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

Sormenjälki Sukella tutkimusaiheisiin 'SuperDCA for genome-wide epistasis analysis'. Ne muodostavat yhdessä ainutlaatuisen sormenjäljen.

  • Siteeraa tätä

    Puranen, S., Pesonen, M., Pensar, J., Xu, Y., Lees, J. A., Bentley, S., ... Corander, J. (2018). SuperDCA for genome-wide epistasis analysis. Microbial Genomics, 4(6). https://doi.org/10.1099/mgen.0.000184