Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing

Whole-genome sequencing (WGS) can identify variants that cause genetic disease, but the time required for sequencing and analysis has been a barrier to its use in acutely ill patients. In the present study, we develop an approach for ultra-rapid nanopore WGS that combines an optimized sample preparation protocol, distributing sequencing over 48 flow cells, near real-time base calling and alignment, accelerated variant calling and fast variant filtration for efficient manual review. Application to two example clinical cases identified a candidate variant in <8 h from sample preparation to variant identification. We show that this framework provides accurate variant calls and efficient prioritization, and accelerates diagnostic clinical genome sequencing twofold compared with previous approaches.

Whole-genome sequencing could save NHS millions of pounds, study suggests

The use of whole-genome sequencing could save the NHS millions of pounds, a study suggests, after it found a quarter of people with rare illnesses received a diagnosis for their condition through the technology.

In some cases, the findings have provided reassurance for families that they have not passed their condition on to their children, while in others they have inspired life-changing treatments.

Advances in Genomics for Drug Development

For over 20 years, genomics has been used as a tool for accelerating drug development. Various conceptual approaches and techniques assist target identification, target prioritization and tractability, as well as the prediction of outcomes from pharmacological perturbations. These basic premises are now supported by a rapid expansion of population genomics initiatives

Long Reads Can Make Short Work of Rare Disease Diagnostics

Why might longer reads improve genetic disease diagnosis? The answer lies, in part, in the types of mutations that cause disease. Some genetic diseases are caused by single nucleotide variants (SNVs), which require a high level of sequencing accuracy to detect—an area where short reads excel. But other deleterious genomic changes are larger and more complex—including large insertions, deletions, translocations, copy number variants, and structural variants. These larger variations can be missed by short reads but detected in longer sequence reads.

Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval

Our work confirms drugs with genetically supported targets were more likely to be successful in Phases II and III. When causal genes are clear (Mendelian traits and GWAS associations linked to coding variants), we find the use of human genetic evidence increases approval by greater than two-fold, and, for Mendelian associations, the positive association holds prospectively. Our findings suggest investments into genomics and genetics are likely to be beneficial to companies deploying this strategy.

Top U.S. Medical Centers Roll Out DNA Sequencing Clinics for Healthy Clients

Genomic sequencing programs that cater to apparently healthy adults have been started in the past few years at the Mayo Clinic; the University of California, San Francisco; and the HudsonAlpha Institute for Biotechnology, a nonprofit research institution in Alabama. Now, two top Boston hospitals are getting into the potentially lucrative business.

Genomics-driven drug discovery based on disease-susceptibility genes

Genome-wide association studies have identified numerous disease-susceptibility genes. As knowledge of gene–disease associations accumulates, it is becoming increasingly important to translate this knowledge into clinical practice. This challenge involves finding effective drug targets and estimating their potential side effects, which often results in failure of promising clinical trials. Here, we review recent advances and future perspectives in genetics-led drug discovery, with a focus on drug repurposing, Mendelian randomization, and the use of multifaceted omics data.

The Advantages of Long-Read Sequencing

DNA sequencing technologies have contributed to drugdiscovery and development pipelines for decades, butmore recent innovations offer to significantly expand theapplications for which sequencing is an appropriate choice. While next-generation sequencing (NGS) instruments were essential for making sequencing more affordable, the short reads they produce are not universally useful. They have beenexcellent for applications such as […]