Dataset Information

D-SCRIPT translates genome to phenome with sequence-based, structure-aware, genome-scale predictions of protein-protein interactions.

ABSTRACT: We combine advances in neural language modeling and structurally motivated design to develop D-SCRIPT, an interpretable and generalizable deep-learning model, which predicts interaction between two proteins using only their sequence and maintains high accuracy with limited training data and across species. We show that a D-SCRIPT model trained on 38,345 human PPIs enables significantly improved functional characterization of fly proteins compared with the state-of-the-art approach. Evaluating the same D-SCRIPT model on protein complexes with known 3D structure, we find that the inter-protein contact map output by D-SCRIPT has significant overlap with the ground truth. We apply D-SCRIPT to screen for PPIs in cow (Bos taurus) at a genome-wide scale and focusing on rumen physiology, identify functional gene modules related to metabolism and immune response. The predicted interactions can then be leveraged for function prediction at scale, addressing the genome-to-phenome challenge, especially in species where little data are available.

SUBMITTER: Sledzieski S

PROVIDER: S-EPMC8586911 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

D-SCRIPT translates genome to phenome with sequence-based, structure-aware, genome-scale predictions of protein-protein interactions.

Sledzieski Samuel S Singh Rohit R Cowen Lenore L Berger Bonnie B

Cell systems 20211009 10

We combine advances in neural language modeling and structurally motivated design to develop D-SCRIPT, an interpretable and generalizable deep-learning model, which predicts interaction between two proteins using only their sequence and maintains high accuracy with limited training data and across species. We show that a D-SCRIPT model trained on 38,345 human PPIs enables significantly improved functional characterization of fly proteins compared with the state-of-the-art approach. Evaluating th ...[more]

PMID: 34536380

Similar Datasets

Project description:BackgroundWhole-genome sequence (WGS) data harbor causative variants that may not be present in standard single nucleotide polymorphism (SNP) chip data. The objective of this study was to investigate the impact of using preselected variants from WGS for single-step genomic predictions in maternal and terminal pig lines with up to 1.8k sequenced and 104k sequence imputed animals per line.MethodsTwo maternal and four terminal lines were investigated for eight and seven traits, respectively. The number of sequenced animals ranged from 1365 to 1491 for the maternal lines and 381 to 1865 for the terminal lines. Imputation to sequence occurred within each line for 66k to 76k animals for the maternal lines and 29k to 104k animals for the terminal lines. Two preselected SNP sets were generated based on a genome-wide association study (GWAS). Top40k included the SNPs with the lowest p-value in each of the 40k genomic windows, and ChipPlusSign included significant variants integrated into the porcine SNP chip used for routine genotyping. We compared the performance of single-step genomic predictions between using preselected SNP sets assuming equal or different variances and the standard porcine SNP chip.ResultsIn the maternal lines, ChipPlusSign and Top40k showed an average increase in accuracy of 0.6 and 4.9%, respectively, compared to the regular porcine SNP chip. The greatest increase was obtained with Top40k, particularly for fertility traits, for which the initial accuracy based on the standard SNP chip was low. However, in the terminal lines, Top40k resulted in an average loss of accuracy of 1%. ChipPlusSign provided a positive, although small, gain in accuracy (0.9%). Assigning different variances for the SNPs slightly improved accuracies when using variances obtained from BayesR. However, increases were inconsistent across the lines and traits.ConclusionsThe benefit of using sequence data depends on the line, the size of the genotyped population, and how the WGS variants are preselected. When WGS data are available on hundreds of thousands of animals, using sequence data presents an advantage but this remains limited in pigs.

Dataset Information

D-SCRIPT translates genome to phenome with sequence-based, structure-aware, genome-scale predictions of protein-protein interactions.

Publications

D-SCRIPT translates genome to phenome with sequence-based, structure-aware, genome-scale predictions of protein-protein interactions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets