WYMM Tour: Bangalore, India

South Asia and India contributes the highest numbers of preterm birth (PTB), the single largest cause of neonatal mortality. PTB is also associated with other health adversities in childhood and in adult life. We conducted a genome-wide association study (GWAS) of spontaneous preterm birth (sPTB) on 6,211 Indian women in the GARBH-Ini cohort followed by cross-ancestry meta-analyses. We identified both population-specific and trans-ethnic genetic associations with sPTB in Indian women. We integrated genotype, long read sequencing, DNA methylation, transcriptome and clinical data to delineate the mechanisms by which the identified SNPs might increase the risk of sPTB. We expect two major public health impacts from our findings. The SNPs and the downstream mechanistic linkages can help us identify potential biological pathways that may be amenable to interventions to prevent sPTB. Further, the set of SNPs identified in our study, might help us stratify pregnant women at risk of preterm birth, thus enabling clinicians to prioritise their antenatal care to improve birth outcomes.

There has been a burst of high-quality genome assemblies of non-model species in the past decade. In this study, we employed a hybrid genome assembly approach to sequence the genome of Lady Amherst’s pheasant, Chrysolophus amherstiae. This is an ornamental pheasant species, which is valued for its elaborate plumage and is bred in captivity across the globe. We use both Illumina short reads along with the Nanopore long-read approach to generate a de novo hybrid genome assembly. We employed both MaSuRCA and WenganD to assemble the genome. We obtained a scaffold-level assembly with N50 ~3.9 Mb and a near-complete BUSCO assessment (96.8%). Comparative analysis with other available pheasant genomes identified significant fluctuations in gene families involved in immune response and visual perception, suggesting the role of sexual selection in shaping genome evolution in sexually dimorphic species. We are currently using the hybrid genome assembly approach to generate multiple de novo genomes of other pheasant species.

Background – The promise of using gut‑microbiome profiles to guide longevity interventions and drive AI‑enabled therapeutics is tempered by a widening credibility gap. Landmark inter‑laboratory surveys and recent editorial critiques have exposed a landscape in which technical artefacts, digital contamination, and divergent bioinformatic choices can overwhelm the biological signal they are meant to reveal. Objective – This talk scrutinises the hidden fracture lines in microbiome science and outlines a pragmatic path toward data sets that clinicians, regulators, and machine‑learning systems can finally trust. Approach – We performed a cradle‑to‑cloud audit of the microbiome workflow, tracing error propagation from sampling and DNA extraction through sequencing and downstream analytics. Replicate studies spanning consumer testing pipelines and academic laboratories were stress‑tested against consensus quality benchmarks developed by the Microbiome Quality Control consortium. Findings – Conventional pipelines often behave like shifting sands: replicate samples fragment into divergent communities, reference databases embed mislabelled sequences, and disease‑prediction models inherit confounders masquerading as mechanistic insight. By re‑engineering each stage—harmonising wet‑lab chemistries, adopting long‑read platforms, and enforcing context‑aware annotation—we replaced that instability with cohesive, self‑consistent outputs that now form the foundation of Decode Biome’s Metagenomic sequencing. Conclusion – Methodical standardisation, not more sequencing, is the missing keystone for microbiome‑guided longevity medicine. Only after grounding the field on reproducible technology can AI unlock its full therapeutic and diagnostic potential.

Oxford Nanopore long-read sequencing (ONT-LRS) is a not only a paradigm shift in genomics research but also has found immense utility in the field of medical genetics. Chromosomal and Mendelian disorders, together considered as rare genetic disorders, affect nearly 1 in 20 Indians. Most of these disorders are the result of small or large genomic variations, some of which are complex and pose substantial diagnostic obstacles. Multitude of tests are often utilized to decipher these variations. However, long reads (ONT-LRS), which span tens of kilobases, as a single test facilitates the comprehensive detection of single nucleotide variations, small indels, structural variants (SVs), large deletions, duplications, repeat expansions, complex rearrangements and methylation abnormalities. Many of the variations such as SVs and complex rearrangements are often missed by short-read technologies.

Additionally, Oxford Nanopore sequencing is particularly adept at resolving variants in regions of segmental duplications. Another significant advantage is the precise phasing of haplotypes, which is crucial for comprehending the inheritance of diseases. Further, Oxford Nanopore sequencing can simultaneously detect epigenetic modifications, such as DNA methylation, providing a deeper understanding of the regulatory mechanisms that are involved in Mendelian disorders. The unique feature that is possible with only ONT-LRS is adaptive sampling, which facilitates sequencing of regions of interest only. This feature is particularly helpful in sequencing sets of genes in their entirety including promoters, deep intronic regions and UTRs simultaneously acting as a ‘snapshot’ of the genome. Its unique ability to sequence directly the full-length transcripts, has enabled superior splice variant detection. These developments result in a higher diagnostic yield, particularly in cases that are more complex.

The presentation will focus on our interesting findings on the applications of Oxford Nanopore sequencing in clinical genetics, particularly inherited neurological disorders.

Genomic characterisation of tumour cells is an essential component of modern risk stratified therapy in B cell precursor Acute Lymphoblastic Leukaemia (BCP-ALL). Transcriptome analysis using short read-NGS approaches has identified more than 25 genomic subtypes. In LMIC settings it is difficult to implement these approaches due to limited resources. Nanopore sequencing promises to be a potential tool to provide rapid cost effective genomic characterisation.

Dairy cattle in India have a large disease burden because of which the dairy industry suffers enormous loss in productivity. To ensure that various disease control measures are effectively used, large-scale population-wide molecular surveillance of pathogens affecting dairy cattle need to be developed, validated and implemented. Towards this requirement my lab has been working on developing various molecular techniques, predominantly using Oxford Nanopore sequencing, to detect, identify and genetically characterized pathogens of interest from animal and environmental samples. In this presentation I will give an overview of the work done on lumpy skin disease and theileriosis as examples of two cattle diseases which we have studied using Oxford Nanopore sequencing. In case of the lumpy skin disease the Indian viral variants have been characterized by whole genome sequencing of the virus, while in case of theileriosis, targeted gene sequencing was carried out to characterize genetic variations responsible for drug resistance affecting treatment outcomes.

At miBiome Therapeutics #GenomicsForAll, we partner with several academic researchers on the use of long-read technology from Oxford Nanopore Technologies (ONT). In this presentation, I will focus on two case studies of whole genome hybrid assembly using ONT and short-read technology (Illumina) for prokaryotes and eukaryotes.

India is a land of rich diversity of food, culture, languages and microbiota. We started the microbiome revolution in India more than a decade back utilizing next generation sequencing based microbiome solutions. BugSpeaks, South Asia’s first microbiome test provides personalized actionable inputs based on the individual’s gut microbiota. BugSpeaks derived personalized nutritional recommendation has been shown to be effective in supplementing treatment of many diseases. Our recent publication shows the efficacy and safety of BugSpeaks’s nutritional recommendation in Type 2 diabetes. I will be sharing some information based on our microbiome journey in India.

Utilisation of sequencing in a real-time hospital setting. We look at which sample types are the most prevalent in the application of microbe identification. From a snapshot of 100 samples, we also compare other identification methods and their comparable outcomes. The general workflow application in a healthcare setting is discussed, along with challenges, resolutions of application, and the subsequent decision-making processes.

Genomics is one of the youngest disciplines of biological sciences, which has made huge strides in the last two decades. It has traversed the path from potential to knowing the information coded within the genomes of organisms to the possibilities of real-time deployment in real-life scenarios. For all its negatives, the COVID-19 pandemic made Genomic Surveillance part of public conversation vocabulary. As we live in the golden age of Genomics, we have a responsibility towards realising its potential for strengthening public health and public good at large, with a fine balance between specificity and sensitivity. In alignment with this, the talk will cover different aspects of “Integrative Genomic Surveillance”-led insights for both the host and the pathogen(s). Especially, the focus will be on the genomics-based findings for the observed differential disease severities (mild, moderate, severe) and clinical outcomes (recovery/mortality) across different infectious diseases with significant burden in India. Incentive for us - How quickly can it reach hospitals where decisions for treatment or prescription of antibiotics are based on Genomics tests? How can we strengthen the fight against AMR?

In this talk, I summarize our results so far in identifying and cataloging structural variants in Indian populations using long read sequencing.