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Nature Papers Compare Targeted Bisulfite Sequencing Platforms, Examine Risk Score Transferability, More

A comparison of five commercially available platforms for targeted bisulfite sequencing (TBS) is presented in Nature Biotechnology this week, offering a resource to help researchers determine the best technology for their needs. TBS has become the method of choice for the cost-effective, targeted analysis of the human methylome at base-pair resolution, but off-the-shelf TBS kits employ different experimental strategies to generate sequencing libraries and differ in the scope of regions they cover. To better understand the strengths and limitations of each, University College London scientists compare five TBS platforms, including three hybridization capture-based ones from Agilent, Roche, and Illumina and two reduced-representation-based ones from Diagenode and NuGen, across 11 samples. They also benchmark each of the five platforms to gold standard data generated using Illumina whole-genome bisulfite sequencing and Nanopore sequencing, evaluate the interoperability of the platforms, and provide guidance for their harmonization.

A study examining the transferability of genetic risk scores (GRSs) to African populations is reported in this week's Nature Medicine. Focusing on GRSs related to lipid traits, a team led by scientists from The African Computational Genomics Research Group evaluated whether GRSs derived from data of African Americans and multiancestry cohorts perform better in sub-Saharan Africans (SSA) than European ancestry-derived scores. Using summary statistics from the Million Veteran Program, they show that GRSs derived from data from African Americans enhance polygenic prediction of lipid traits in SSA compared to European and multiancestry scores. Notably, they find poor transferability of these GRSs between South African Zulu and Ugandan populations, possibly due to differences in environmental and genetic factors, highlighting the need for more efforts to optimize polygenic prediction in Africa.

An atlas of adult neurogenesis in primates, generated through single-cell RNA sequencing of the macaque hippocampus, is reported in this week's Nature Neuroscience. While there is abundant evidence that a substantial number of new neurons are generated in the brains of adult rodents, it remains largely unknown whether and how adult neurogenesis occurs in primates. To investigate, a group led by researchers from Sun Yat-sen University used an optimized scRNA-seq pipeline to profile 207,785 cells from the adult macaque hippocampus, identifying 34 cell populations comprising all major hippocampal cell types. They also identify stem cell specification trajectories for both granule cells and neuroglia with novel intermediate populations. The scientists further confirm that neurogenesis is recapitulated in ex vivo neurosphere cultures from adult primates, supporting the existence of neural precursor cells that are able to proliferate and differentiate. "If adult primate neurogenesis exists, it will be considerably different from the other species," they write. "Comparative studies between primates and rodents may be necessary for a further understanding of underlying mechanisms for adult neurogenesis in primates."