A research team comprising of scientists from the Agency for Science, Technology and Research’s (A*STAR) Genome Institute of Singapore (GIS), clinicians from Tan Tock Seng Hospital (TTSH), and researchers from the National University of Singapore (NUS) have discovered a way to study gut bacteria.
This advancement in the fight against antibiotic resistance uses portable DNA sequencing technology and complex algorithms to conduct observations on multiplex bacterial communities residing in the gut. It will combine the genetic code of the various bacterial communities to trace the spread of antibiotic resistance and how it affects human health.
The research team, led by Professor Niranjan Nagarajan and Dr Denis Bertrand from GIS, trialled with various technologies before discovering this method. Their breakthrough happened when they found a portable DNA nanopore sequence that allows for long DNA ‘reads’ and high data throughput.
Only after evaluating 197 stool samples from current clinical studies had they calibrated a method that would allow them to study a large sample size of microorganisms with high-quality data.
This information allowed the team to create a hybrid assembly algorithm, OPERA-MS, that combines billions of DNA sequences into individual strain genomes within the microbial community.
OPERA-MS is a combination of a complex Bayesian clustering algorithm and combinatorial optimisation which can solve perplexing DNA puzzles that metagenomes represent.
Metagenomics is used to study DNA from environmental samples and understand the microbial community existing within them. The metagenome of an environmental sample is made up of the genomes of each organism within the sample.
Prof Niranjan Nagarajan, Associate Director and Senior Group Leader at GIS, noted, “The complete genome sequence of an organism is its ultimate fingerprint. We are excited to now be able to extract it directly out of metagenomic data. We need powerful technological capabilities like this to successfully apply clinical metagenomics in the battle against antibiotic resistance.”
Today, antibiotic-resistant microorganisms pose a big threat to many healthcare systems. It is likely to have affected more 10 million lives annually and result in a deficit of more than 100 trillion US dollars to the global economy by 2050.
Benefits
Our gut hosts trillions of bacteria which help us in many ways:
- Breaking down undigested food
- Produce essential vitamins and nutrients
- Train the immune system
Threat
The gut, however, also acts as a stagnant house for antibiotic-resistant bacteria. As a result, symptoms will not be shown for a long time and this resistant behaviour will be transferred to other bacteria.
With the discovery of this new form of study, it gives a more complete genomic map for scientists to be able to study the effect of individual bacterial strains on the function of a microbial community within the human body.
The research team found that OPERA-MS provides up to 10 times more complete genomes when using short reads and at least 5 times more accurate genomes than those produced by long reads.
Dr Denis Bertrand, Staff Scientist at GIS and lead author of this work said, “Hybrid metagenomic assembly with OPERA-MS provides unprecedented resolution at the strain level and near-complete genomes from uncultured samples. We believe this approach can serve as the basis of gold-standard metagenome-assembled genomes for future studies.”
