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Innovation through collaboration: the Whole Genome Sequencing (WGS) experience



Letizia Goretti, Senior Director, Transactions & Alliances, Genomics and Nano-Electronics, Johnson & Johnson Innovation and Mary Helen Black, Head of Population Analytics, Janssen Research & Development

On November 17th, the world’s largest single release of Whole Genome Sequencing (WGS) data from 200,000 UK Biobank participants was made available to researchers through the recently launched UKB Research Analysis Platform. Johnson & Johnson, along with Amgen, AstraZeneca and GlaxoSmithKline (GSK), came together in 2019 with the Wellcome Trust and the government’s UK Research and Innovation agency to fund this breakthrough £200M project aimed at sequencing the complete genetic code of 500,000 UK Biobank volunteers. In this article Letizia Goretti, Senior Director, Transactions & Alliances, Genomics and Nano-Electronics at Johnson & Johnson and Mary Helen Black, Head of Population Analytics for Janssen Research & Development, who led the strategic and scientific sides of the project reflect on the experience so far.

How are these data important for understanding and advancing drug discovery and human health?

MHB: First, WGS data linked to detailed clinical and lifestyle information can help accelerate drug discovery and development by allowing researchers to identify new drug targets. WGS data allow for identification of very rare gain- and loss-of-function variants that contribute to disease onset and progression. From this, we may infer that inhibiting or agonizing the product of the gene containing these variants can be used to treat disease. WGS also allows us to detect rare, non-coding variants; these variants help us understand gene regulation and more of the biology underlying disease, but also yield non-coding RNAs that can be targeted by new therapies. Finally, these data allow us an opportunity to understand the functional impact of structural variations such as short tandem repeats, which can be used to further understand the etiologies of complex diseases. Altogether, this will allow answering questions such as why some individuals develop a disease but others do not and why some chronic conditions worsen over time. Then, these data also allow us to predict target-associated liabilities. We can mine these data to better inform our therapeutic area partners and nonclinical safety teams about how likely it is that modulating a target in a particular way will result in a therapeutic effect or will potentially cause adverse events, before a drug is ever tested in the clinic.

Who will be able to access these data?

MHB: Researchers worldwide may register with the UK Biobank to apply for access to the data and perform analysis on the Research Analysis Platform.

LG: The size and scale of the data is truly unprecedented, while generating the data, we also had to overcome the challenge of storage and access for its massive size. Alongside the platform developed by UKB, we at Janssen built a fit for purpose computational ecosystem for data storage and large-scale analysis for projects in-house.

Which therapeutic areas do you think these data are going to impact the most?

MHB: We already have several ongoing projects with our therapeutic area partners that will impact programs in immunology, renal disease, and neurodegeneration.

LG: The availability of these data is driving scientific engagement and collaboration between Janssen therapeutic areas. We’ve put a significant effort into building internal scientific engagement and collaboration between our Population analytics group and different therapeutic areas at Janssen, so now everyone is aware of the capabilities and the value it may bring.

What are the major strengths of this collaborative project?

LG: This project had contributions from the UK government, charity organizations, sequencing providers, and other pharma companies. We are giving credence that these broad collaborations with very different stakeholders around the table are possible, we proved that we could work together to deliver on time and on budget, despite the odds. For these reasons, we are all incredibly proud of this achievement, especially knowing the challenges and roadblocks the pandemic has caused on our program.

MHB: Having this level of genomic data tied to detailed clinical information on this population size allows for the interrogation of many research questions. Being able to use those data to understand the biological underpinnings of disease to potentially better treat diseases is an incredibly valuable resource unlike anything else that exists today.

What are the next steps?

MHB: The full 500,000 whole-genome sequences will be available to consortium partners including Janssen in 2022. From a scientific standpoint, the genome alone will not answer all of our questions. To this end, we have partnered with UK Biobank and a consortium of pharma partners to undertake a proteomics study in ~56,000 participants of UK Biobank. This type of study has the ability to give us invaluable insights into the consequences of genomic variation and its effects on disease. Multi-omics is the future, and it’s key to understanding disease onset and progression and accelerating development of more efficacious treatments. Furthermore, another priority for the future is to expand the ethnic diversity of the population-based data we analyze. In UK Biobank, 88% of the cohort is white British. However, among the ~7,000 individuals that have African ancestry, there are important differences in allele frequencies in known and putative disease genes, and we have learned a lot from the diversity that does exist in UK Biobank. The next step will be to expand our investigation, perhaps with other collaborations, to better interpret the data and understand the burden of disease associated with loss of function variants in diverse populations

LG: Our hope is that this will help to build trust that these partnerships, even with such diverse group of stakeholders, can really happen and deliver to their promises to ultimately advance human health.

To find out more about the collaboration, you can read the press release here.

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