Researchers at the University of California San Diego (USA) have developed an approach that uses machine learning to identify and predict which genes make infectious bacteria resistant to antibiotics.
The approach was tested on strains of Mycobacterium tuberculosis – the bacteria that cause tuberculosis (TB) in humans. It identified 33 known and 24 new antibiotic resistance genes in these bacteria.
The researchers say the approach can be used on other infection-causing pathogens, including staph and bacteria that cause urinary tract infections, pneumonia and meningitis. The work was recently published in Nature Communications.
The team trained a machine learning algorithm using the genome sequences and phenotypes – the physical traits or characteristics that can be observed, such as antibiotic resistance – of more than 1,500 strains of M. tuberculosis. From these inputs, the algorithm predicted a set of genes and variant forms of these genes, called alleles, that cause antibiotic resistance. 33 were validated with known antibiotic resistance genes, the remaining 24 were new predictions that have not yet been experimentally tested.
The researchers further analyzed the algorithm’s predictions and identified combinations of alleles that could be interacting together and causing a strain to be antibiotic resistant. They also mapped these alleles onto crystal structures of M. tuberculosis proteins (published in the Protein Data Bank). They found that some of these alleles appeared in certain structural regions of the proteins.
The results of this study are all computational, so the team is looking to work with experimental researchers to test whether the 24 new genes predicted by the algorithm indeed confer antibiotic resistance in M. tuberculosis.
Future studies will involve applying the team’s machine learning approach to the leading infectious bacteria, known as the ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species. As a next step, the team is integrating genome-scale models of metabolic networks with their machine learning approach to understand mechanisms underlying the evolution of antibiotic resistance.