Results from a National Human Genome Research Institute effort to identify future research priorities and opportunities in human genomics, particularly in the context of health, are presented in Nature this week. Through the NHGRI's Forefront of Genomics initiative, the institute held more than 50 events over the past two years to collect input from stakeholders for an updated strategic vision for human genomics research. In a Perspective piece, NHGRI representatives describe a four-area framework for its vision including guiding principles and values to steer research efforts; a robust foundation for genomics that includes infrastructure, resources, and technology development; breaking down technical and other barriers that impede progress genomics; and compelling genomics research projects such as ones that extend multi-omic studies of human disease and health into clinical settings. "With the 2020 strategic vision described here providing a thoughtful guide and with enduring feelings of wonder, urgency, ambition, and social consciousness providing unfettered momentum, we are ready to embark on the next exciting phase of the human genomics journey," the representatives write. GenomeWeb has more on this here and has a Q&A with NHGRI Director Eric Green here.
A method for analyzing RNA structure using nanopore sequencing is reported in Nature Biotechnology. Current methods for determining RNA structure with short-read sequencing are unable to differentiate between distinct transcript isoforms, scientists from the Genome Institute of Singapore write in the study. As an alternative, the team developed an approach — called PORE-cupine — that combines structure probing using chemical modifications with direct long-read RNA sequencing and machine learning to detect secondary structures in cellular RNAs. It also captures global structural features, such as RNA-binding-protein binding sites and reactivity differences at single-nucleotide variants. Although PORE-cupine requires an aggregate of signals across many strands to obtain accurate structure reactivity information, further refinement, such as by increasing the modification frequency per strand and improving sequencing and analytical techniques, could allow for its use in studying RNA structures at the single-molecule level, the researchers conclude.
A patient's immune response to SARS-CoV-2 declines after three months and depends largely on the severity of infection, according to a report appearing in Nature Microbiology. The findings suggest that vaccine boosters may be required to maintain long-term protection. In the study, a team led by King's College London scientists tracked the antibody responses of 59 SARS-CoV-2 patients and 37 healthcare workers for three months following the onset of their symptoms. "We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titers observed after an initial peak, and that the magnitude of this peak is dependent on disease severity," they write. Some people with severe infections maintained high levels of neutralizing antibodies for more than 60 days after their symptoms arose, while the immune responses of those with milder disease returned to baseline levels relatively quickly. The findings, the study's authors state, highlight the issues of reinfection and vaccine protection durability facing efforts to address the pandemic.
A mutation in the SARS-CoV-2 spike protein plays a key role in the virus' spread and may be a potential target for drug interventions, a study in this week's Nature suggests. The spike protein mutation, called D614G, has become dominant during the pandemic, but its effect on SARS-CoV-2 transmission and potential vaccines is unclear. To investigate, scientists from the University of Texas Medical Branch compared the effects of SARS-CoV-2 strains either lacking or harboring the mutation in hamsters. They find that D614G led to higher infectious titers in nasal washes and the trachea but not the lungs, supporting clinical evidence that the mutation enhances viral loads in the upper respiratory tract in those infected with SARS-CoV-2, potentially increasing transmission. Noting that all SARS-CoV-2 vaccines under development are based on the original strain of the virus that lacks the D614G mutation, the researchers also examined the effect of neutralizing antibodies against the strain with the mutation. Unexpectedly, those antibodies appeared to have slightly greater effect on the D614G-carrying virus, showing that the mutation is not likely to affect the efficacy of vaccines in development.