London Calling 2020

London Calling this year took a very different format, going online for the first time ever. With over 5,500 people tuning in to see the action, either live or on-demand, it was a fantastic two-and-a-half days of presentations, discussion and networking.

All of the presentations are available on demand for you to watch back, and you can access full write ups in the Community — here are a just few highlights from the plenary talks.

Genomic epidemiology panel: Joseph Fauver, Estee Torok, George Githinji, Jing Lu

Experts in epidemiology came together from across the world to discuss the sequencing-based response to the COVID-19 outbreak in the Kenya, China, the UK and the US.

Joseph Fauver spoke about coast-to-coast spread of SARS-CoV-2 during the early epidemic in the United States, using phylogenetic data to establish that the first cases introduced to Connecticut were the result of domestic rather than international travel. Joseph's team were able to turn full genomes around with 24hrs of sample receipt, allowing them to track lineage and routes of introduction.

Comparison of the ways in which SARS-CoV-2 has arrived in certain locations was a common theme to the talks, with Estée Török investigating community and healthcare-associated introductions, and using this data to demonstrate how genomic epidemiological analysis could inform control measures in the UK. Control measures in China are slightly further along in the outbreak process, with Jing Lu presenting data from the original emergence of SARS-CoV-2 in January 2020. Jing Lu noted that three key strategies have been employed in Guangdong to successfully contain the epidemic: extensive testing, active tracing and strict isolation - but phylogenetic data has enabled the CDC team to identify that most detected cases were linked to travel instead of local community transmission.

The final speaker was George Githinji from KEMRI in Kenya, whose SARS-CoV-2 work has focused on capacity-building for outbreak surveillance across East Africa. An experienced nanopore user, George and his team were able to sequence their first SARS-CoV-2 genomes in April, just days after the first case was identified in Kenya, as well as supporting public health laboratories in 17 other African countries to do the same.

All four speakers, plus guest panel member Nick Loman, came together to discuss a global perspective on the outbreak - comparing approaches across the world and tackling critical issues such as widespread data sharing for accelerated pandemic response.

Dafni Glinos, New York Genome Center

Dafni Glinos opened the conference on Thursday with her work on the largest human long-read cDNA dataset produced to date, consisting of 70 human samples across 15 different tissues. The extensive project leveraged nanopore reads to allow quantitative analysis of isoform expression, revealing widespread allele-specific transcript structure events. In totality, the team identified a staggering 100,000 candidate novel transcripts for known genes, and a further 200 putative novel genes.

The core concept of this work was further supported in the Human Transcriptomics breakout session, featuring speakers Ying Chen, Ricardo De Paoli-Iseppi and Chenchen Zhu discussing the role of alternative splicing in cancer, neuropsychiatric disorders and cardiomyopathies.

Tracy Murphy, Princess Margaret Cancer Center

Tracy Murphy joined us on Friday to talk about the role of nanopore sequencing in mixed lineage leukaemia, a challenging disease to diagnose featuring over 135 different known rearrangements involving 94 distinct partner genes. The current approach for examining these cases is use of cytogenetics, which Tracy projected could be replaced by nanopore sequencing in the future. Her work demonstrated identification of complex translocations at breakpoint-level precision, as well as differential methylation calling between MLL samples. The ideal situation, Tracy described, would be to be able to perform tailored minimal residual disease monitoring over patients over time - a vision which this work marks progress towards.

Benedict Paten, University of California, Santa Cruz

Benedict Paten explored two key areas of human genomics in his talk - assembly and "diplotyping" (a combined phasing and genotyping approach). Introducing new human genome assembler Shasta, Benedict showed results achieving a whopping 58 Mb N50 in an extremely short turnaround time. With the addition of some ultra-long nanopore data, telomere-to-centromere chromosome arm assembly was possible for the majority of chromosome arms.

In addition, using their diplotyping approach, SNV calling performance "was actually better than short-read [data]...which is really exciting".

Concluding a fantastic human genomics presentation, Benedict explained ‘Genomics is failing on diversity –we need to increase the number of complete genomes that we have from a diversity of different human populations, to more fully understand our genetic heritage’.

Ariel Gershman, Johns Hopkins

The final plenary of the conference came from Ariel Gershman, whose studies of the hummingbird genome act as a system for exploring metabolic disease in humans. Using a few flow cells on a single PromethION, Ariel generated long and ultra-long nanopore data to produce a highly contiguous, highly accurate, and highly complete hummingbird genome, as well as a full long-read transcriptome. This unprecedented profiling of the wild hummingbird genome will be pushed even further in future with the additional of differential methylation data.