Availability of benign missense variant "truthsets" for validation of functional assays: Current status and a systematic approach.

Multiplex assays of variant effect (MAVEs) provide promising new sources of functional evidence, potentially empowering improved classification of germline genomic variants, particularly rare missense variants, which are commonly assigned as variants of uncertain significance (VUSs). However, paradoxically, quantification of clinically applicable evidence strengths for MAVEs requires construction of "truthsets" comprising missense variants already robustly classified as pathogenic and benign. In this study, we demonstrate how benign truthset size is the primary driver of applicable functional evidence toward pathogenicity (PS3).

Quantifying evidence for phenotypic specificity (PP4) for syndromic phenotypes: Large-scale integration of rare germline FH variants from diagnostic laboratory testing for HLRCC (Hereditary Leiomyomatosis and Renal Cell Cancer) and renal cancer.

Purpose: Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a rare cancer susceptibility syndrome exclusively attributable to pathogenic variants in FH (HGNC:3700). This paper quantitatively weights the phenotypic context (PP4/PS4) of such very rare variants in FH.

Methods: We collated clinical diagnostic testing data on germline FH variants from 387 individuals with HLRCC and 1,780 individuals with renal cancer, and compared the frequency of 'very rare' variants in each phenotypic cohort against 562,295 population controls.

The interplay between temperature and growth phase shapes the transcriptional landscape of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a highly versatile bacterium capable of surviving and often thriving in stressful environmental conditions. Here we report the effect of two environmental conditions, temperature and growth phase, on the P. aeruginosa PAO1 transcriptome.

Chromosome-scale genome assembly and gene annotation of the hydrothermal vent annelid Alvinella pompejana yield insight into animal evolution in extreme environments.

Background: The Pompeii worm Alvinella pompejana, a terebellid annelid, has long been an exemplar of a metazoan that lives in an extreme environment, on the chimney wall of deep-sea hydrothermal vents, but this very environment has made it difficult to study. Comprehensive assessment of Alvinella pompejana genome content, and the factors that could explain its ability to thrive in seemingly hostile conditions has been lacking.

Results: We report the chromosome-level genome sequence of Alvinella pompejana and population-level sequence variants.

Not just species recording: the potential of citizen science for habitat monitoring.

Context: Reversing the global biodiversity crisis requires not only conservation and management of species, but the habitats in which they live. While there is a long history of biodiversity recording by volunteers, at least in Europe, information on habitats is less frequently recorded. Habitat data is needed to map and monitor habitat extent and condition; to train and validate earth observation (EO) data; and to explain biodiversity change.