WYMM Summit: MEAI 2025

Since its inception in 2020, the Africa CDC Pathogen Genomics Initiative has spearheaded the implementation of a continental genomic surveillance scheme across Africa Union Member States. The Africa PGI has trained over 400 public health professionals through targeted fellowships and workshops, building a cadre of public health professionals capable of handling biosafety-compliant sample collection to cloud-based data pipelines. More than 40 (70%) of AU member state’s reference labs have been equipped with genomic sequencers, enabling real-time variant tracking during outbreaks like Ebola, Mpox and Cholera. The successes of the initiative have highlighted the imperative of genomic surveillance being urgent for (i) detecting emerging pathogens, (ii) guiding outbreak response, (iii) tracking variants, and (iv)informing public health interventions. We present a candid examination of experiences and insights from capacity building across the whole surveillance continuum—from specimen collection, through laboratory sequencing, to bioinformatics and data interpretation. The implementation experience challenges the conventional narrative, moving beyond the idealized framework of "plug-and-play" technology to explore the complex, often-unseen human and logistical factors that define the success of a continental-scale scheme. We will delve into how building capacity is not merely about providing equipment and reagents but about nurturing a sustainable ecosystem of skilled professionals, fostering inter-regional collaboration, and establishing resilient logistical pathways. Further, we explore the vulnerabilities in the supply chain ecosystem, and a lack of unified data governance can derail even the most sophisticated technological deployments. We conclude that, while the technology is powerful, the ultimate success of our efforts rests on our ability to navigate the messy, unpredictable terrain of human and systemic integration. We advocate for collective focus from tool perfection to building resilience of the system it inhabits, through iterative adaptive increments to ultimately chart a more effective course for health security across Africa and beyond.

Africa has the highest age adjusted cancer mortality rates globally and cancer incidence in Africa is expected to double by 2040. Despite this growing disproportionate burden of disease, African cancer patients are woefully understudied. The people of African descent remain significantly underrepresented in cancer research, accounting for less than 3% of globally available genomic data and are often the least well served by advances in precision medicine. Yemaachi is addressing this gap by building The African Cancer Atlas (TACA). This is an Africa-centred but globally facing initiative - providing much needed biological and clinical data to drive the next generation of more inclusive drug discovery. We have an oncology partner network across 9 geographically dispersed African countries with standardised protocols for sample collection and processing across multiple sites. Our unique cloud-based clinical data management platform facilitates the collection of longitudinal clinical metadata from across our network into a unified clinico-demographic database. We have initiated extensive genomic profiling of various cancer types among African patients to investigate how population-specific genetic variation contributes to cancer risk, identifying novel driver mutations, somatic copy number alterations (SCNAs) and mutational signatures that can point to disease-relevant environmental exposures or impaired core biological pathways. This project is supported by a first-of-its-kind partnership between African biotech and global pharma and represents one of the most ambitious genomics undertakings in Africa - Building the most diverse cancer genome database in the world. Oxford Nanopore Technologies provides an opportunity to supercharge TACA, through more accurate identification of structural variants and the ability to generate epigenetic data in parallel with genomic sequencing. Leveraging the scalability of the Oxford Nanopore platform we are also integrating NGS into paediatric leukaemia care in Ghana – a significant leapfrog. “What you miss (really) matters” – and with TACA we aim to ensure that African populations are no longer missed out from cancer drug discovery.

Oxford Nanopore Technologies (ONT) has introduced a paradigm shift in genomics with real-time, long-read sequencing, but its designation as a research-use-only platform has limited its clinical adoption. This talk presents the journey of the genomics lab at LifeCore - achieving both CAP (June 2024) and ISO 15189 (January 2025) accreditation for whole genome sequencing using ONT.

Established in 2021 within a multidisciplinary longevity and wellness-focused private clinic, LifeCore’s genomics unit was built from the ground up to integrate ONT WGS into clinical diagnostics. We will outline the strategies used to overcome the technical, regulatory, and operational challenges of implementing a non-IVD platform in a clinical setting. This includes rigorous analytical validation, bioinformatics optimization, reproducibility testing, and alignment with international quality standards.

Our experience bridges the gap between innovation and regulation - offering a replicable blueprint for other laboratories seeking to clinically adopt ONT. As far as we are aware, LifeCore remains the only lab in the Middle East providing clinical-grade reports using ONT WGS, addressing a critical need for advanced genomic diagnostics in a rapidly evolving healthcare ecosystem.

I will delve into translating ONT into a regulatory-compliant pipeline, how to navigate accreditation audits for non-standard platforms, and why ONT’s speed, accessibility, and scalability make it a viable clinical tool. The talk will also highlight ONT’s potential role in enabling personalized medicine at scale, especially in regions with growing demand and limited local genomic infrastructure.

There are 100 million Africans living with a rare disease, the majority still undiagnosed. In many countries, the necessary medical genetic services and laboratory testing infrastructure is insufficient to serve the needs of these families. The Undiagnosed Disease Programme in South Africa was established 4 years ago to address this gap. The sequencing technology used within the UDP has evolved over time, with an ever increasing need for more comprehensive testing. Currently, our diagnostic genetic testing service is very limited: for example, in addition to the absence of single-gene testing or gene panels, we also do not have access to chromosomal microarray or MS-MLPA for Beckwith-Weidemann syndrome. Oxford Nanopore long-read WGS has provided us with a game-changing opportunity to diagnose the undiagnosed, to discover novel variants in our underserved and understudied population, and to implement precision medicine in Africa. We are also building robust evidence for the applicability and utility of Oxford Nanopore lrWGS in the clinic in preparation for policy change.

This talk will go over the clinical applications of Oxford Nanopore sequencing and the outlook for its role in the diagnosis of and screening for rare diseases. I will highlight how this technology has the potential to enhance diagnostic yield, shorten the time-to-diagnosis and simplify laboratory workflows leading to more efficient and cost-effective operations.

I will also provide examples on how long read sequencing supports the discovery of novel disease genes.

The unprecedented developments in genome sequencing technologies in the last decade has revolutionized the sequencing of prominent eukaryotic genomes from both animal and plant kingdoms. While the short-reads dominated the first phase of genome sequencing revolution, long-reads are currently driving genomic projects across the world. Among these, Oxford Nanopore Technologies (ONT) has emerged as the most affordable and user-friendly long-read sequencing technology. We are among the pioneers in India in genome sequencing of plant, animal and bacterial genomes. We have performed the first-ever sequencing of genomes of the national bird (Peacock), national animal (Tiger), national tree (Banyan), and several medicinal plants including Aloe vera, Turmeric, Jamun, Amla, Tamarind, Giloy, and fruit trees like Custard apple, Jamun, and other prominent genomes such as Water hyacinth etc. The sequencing of these genomes was followed by robust computational analysis and were published in high—impact journals along with wide media coverage. Initially, we had used a hybrid sequencing approach involving both short and long reads and have gradually shifted towards majorly using the long-reads by ONT technology which has been really helpful in constructing chromosomal-level and telomere to telomere level assemblies. We are also using long-reads for our recent metagenomic projects. I will highlight the major genomic projects and the challenges that still exists in genome sequencing and analysis in this meeting.

High-throughput sequencing (HTS) has revolutionized the study of plant viral and viroid pathogens, providing unprecedented insights into their diversity, evolution, and regional prevalence. HTS has revealed mixed viral infections in major crops and identified water sources as reservoirs of plant viruses, emphasizing its value for epidemiological surveillance and resistance breeding. Globally, the potential of HTS for routine diagnostics has been highlighted in recent research, which also stresses technical challenges and the need for standardized workflows to support plant health certification. Oxford Nanopore Technologies (ONT) has further accelerated field applications of HTS, enabling rapid diagnostics and whole-genome sequencing.

In Kazakhstan, ONT-based studies of plant viruses have been particularly impactful: they defined a novel genetic clade of Raspberry Bushy Dwarf Virus (RBDV), characterized Beet Necrotic Yellow Vein Virus (BNYVV) and Beet Cryptic Virus 2 (BCV2) co-infections, and reported the first detection of Grapevine Yellow Speckle Viroid-1 (GYSVd-1) and Hop Stunt Viroid (HSVd) in grapevine—advancing regional phytosanitary surveillance. These analyses not only revealed a novel clade unique to Kazakhstan, distinct from known isolates, but also identified variable sites in key viral proteins, underscoring their potential role in viral adaptation and pathogenicity.

Post COVID-19, the world has seen the integration of researchers and the public at large, which has strengthened public health decision making. This has been strengthened with the democratisation of genomics from classes to masses. This revolution has been captured in the concept of "MicroLabs" which are essentially built on two concepts of sequencing of priority pathogens in resource limited settings and taking sequencer to the samples rather than samples to the sequencer. This has greatly aided timely detection of pathogens, especially their evolutionary trajectory. My talk will be sharing success stories from the land of 1.4 billion people highlighting benefits of Smart Sustainable Sustained Surveillance. It will also touch upon the aspect of INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) wherein the core is to transfer the research benefits to the community after developing insights from genomic surveillance at the clinical and community level.

Oxford Nanopore sequencing has rapidly emerged as a transformative technology for ecological and evolutionary research, offering real-time, portable, and cost-effective genomic analysis. In our lab, we have applied this technology across diverse systems to address fundamental questions in biomonitoring, conservation, and eco-evolutionary biology. As part of India’s Deep Ocean Mission, we used metagenomic approaches to characterise the previously unexplored virome of the Indian Exclusive Economic Zone (EEZ). From 13 deep-sea samples, we assembled 21,180 viral contigs, identifying 11 sub-families and 15 families spanning two classes (Caudoviricetes and Megaviricetes). Notably, the majority of these assemblies could not be assigned to known taxa, indicating that a substantial proportion of the recovered viral genomes are novel. We also employed nanopore sequencing for avian influenza surveillance. By sequencing amplified viral fragments, we detected environmental viral loads and identified Highly Pathogenic Avian Influenza (HPAI) variants, demonstrating its utility as an early-warning system for zoonotic threats. In another application, dietary metabarcoding of insectivorous bats revealed diverse prey compositions, including six major pests of rice and sugarcane. These findings underscore the critical ecosystem services provided by bat populations, which are increasingly threatened by human activities. At the genome level, we sequenced two air-breathing catfishes (Clarias gariepinus and C. dussumieri) to investigate the genomic basis of terrestrial adaptation and the invasive success of clariids. Furthermore, using only Oxford Nanopore long-read data, we achieved a telomere-to-telomere (T2T), gapless genome assembly for the Himalayan golden mahseer (Tor putitora), a tetraploid species of high conservation concern—a milestone in freshwater fish genomics. Across these projects, we utilised multiple Oxford Nanopore platforms (GridION, PromethION) and a variety of sequencing strategies.

Dr Abdul Karim Sesay PhD, MBE, Assistant Professor and the Head of the Genomics Strategic Core platform at the MRC Unit, The Gambia at London School of Hygiene and Tropical Medicine has been successful in identifying and exploring new projects and equipment, with early access to cutting edge technology, MAP and a VIP utilising Oxford Nanopore Technology (ONT) since 2014. The continuous investment has paid off spectacularly as demonstrated by establishment of genomics core, and the unit and MRCUK funding, effort and success with sequencing Covid-19 positives isolate in The Gambia, working with Ministry of Health NPHL and having a direct impact in the country pandemic response. And in addition, the ongoing collaboration and support of our west African partners in establishing the local capacity to perform sequencing thus achieving decentralization and spreading of ownership and strengthening genomics in our sub-region. Recently the genomics platform at MRCG and ONT have developed a framework to establish a CoE building on previous genomic success in the region. The partnership between Oxford Nanopore and MCRG at LSHTM builds on previous collaborations, including a programme during COVID which built genomics sequencing capacity in eight laboratories across six west African countries. Most recently the two organisations collaborated to sequence over 200 genomes and epigenomes, becoming the first on the continent to achieve such a milestone.

Acute Lymphoblastic Leukaemia (ALL) is characterised by sentinel chromosomal abnormalities including aneuploidies and chromosomal rearrangements that produce chimeric fusion transcripts. Secondary genetic abnormalities including copy number abnormalities and sequence mutations contribute to leukaemogenesis and can either be present at diagnosis or be enriched at relapse.

Genomic characterisation of tumour cells is an essential component of modern risk stratified therapy in B cell precursor Acute Lymphoblastic Leukaemia (BCP-ALL). Currently multiple techniques are used to classify BCP-ALL patients like karyotyping, FISH, MLPA, SNP arrays, PCR based tests to capture the entire spectrum of genetic abnormalities in 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.

Oxford Nanopore sequencing promises to be a potential tool to provide rapid cost-effective genomic characterisation. Unlike traditional sequencing methods Oxford Nanopore sequencing technology allows for the real time analysis of long DNA strands providing both the identification and quantification of genetic variants. Also, adaptive sequencing allows to sequence the whole genome and at the same time enrich the sequencing of genes of interest.

We used nanopore-based transcriptome sequencing in 200 acute leukaemia samples to identify the immunophenotype and genomic subtypes based on gene expression signatures, copy number abnormalities and fusion transcripts. Adaptive sequencing using DNA from leukaemia samples in more than 100 patients has shown excellent concordance in identifying the genomic subtypes.

Oxford Nanopore sequencing is a promising tool to classify acute leukemias based on lineage and identify genomic subtypes of BCP-ALL, the portability and low cost of the platform being the other advantages making implementation feasible in LMICs.