Inferring the heritability of bacterial traits in the era of machine learning

Author:

Mai T Tien1ORCID,Lees John A23ORCID,Gladstone Rebecca A4ORCID,Corander Jukka456ORCID

Affiliation:

1. Department of Mathematical Sciences, Norwegian University of Science and Technology , Trondheim 7034, Norway

2. European Molecular Biology Laboratory, European Bioinformatics Institute EMBL-EBI , Hinxton CB10 1SD, UK

3. Department of Infectious Disease Epidemiology, MRC Centre for Global Infectious Disease Analysis, Imperial College London , London W2 1PG, UK

4. Department of Biostatistics, University of Oslo , Oslo 0372, Norway

5. Department of Mathematics and Statistics, University of Helsinki , Helsinki, Finland

6. Pathogens and Microbes, Wellcome Sanger Institute , Hinxton CB10 1SD, UK

Abstract

AbstractQuantification of heritability is a fundamental desideratum in genetics, which allows an assessment of the contribution of additive genetic variation to the variability of a trait of interest. The traditional computational approaches for assessing the heritability of a trait have been developed in the field of quantitative genetics. However, the rise of modern population genomics with large sample sizes has led to the development of several new machine learning-based approaches to inferring heritability. In this article, we systematically summarize recent advances in machine learning which can be used to infer heritability. We focus on an application of these methods to bacterial genomes, where heritability plays a key role in understanding phenotypes such as antibiotic resistance and virulence, which are particularly important due to the rising frequency of antimicrobial resistance. By designing a heritability model incorporating realistic patterns of genome-wide linkage disequilibrium for a frequently recombining bacterial pathogen, we test the performance of a wide spectrum of different inference methods, including also GCTA. In addition to the synthetic data benchmark, we present a comparison of the methods for antibiotic resistance traits for multiple bacterial pathogens. Insights from the benchmarking and real data analyses indicate a highly variable performance of the different methods and suggest that heritability inference would likely benefit from tailoring of the methods to the specific genetic architecture of the target organism.Availability and implementationThe R codes and data used in the numerical experiments are available at: https://github.com/tienmt/her_MLs.

Funder

European Research Council

Norwegian Research Council

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Embryology,Anatomy

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