A unified analysis of evolutionary and population constraint in protein domains highlights structural features and pathogenic sites

Protein evolution is constrained by structure and function, creating patterns in residue conservation that are routinely exploited to predict structure and other features. Similar constraints should affect variation across individuals, but it is only with the growth of human population sequencing that this has been tested at scale. Now, human population constraint has established applications in pathogenicity prediction, but it has not yet been explored for structural inference. Here, we map 2.4 million population variants to 5885 protein families and quantify residue-level constraint with a new Missense Enrichment Score (MES). Analysis of 61,214 structures from the PDB spanning 3661 families shows that missense depleted sites are enriched in buried residues or those involved in small-molecule or protein binding. MES is complementary to evolutionary conservation and a combined analysis allows a new classification of residues according to a conservation plane. This approach finds functional residues that are evolutionarily diverse, which can be related to specificity, as well as family-wide conserved sites that are critical for folding or function. We also find a possible contrast between lethal and non-lethal pathogenic sites, and a surprising clinical variant hot spot at a subset of missense enriched positions

Lessons learned from organizing and teaching virtual phylogenetics workshops

No abstract available

Conservação de café torrado e moído durante o armazenamento. Parte 2: Massa específica e porosidade

The determination of physical properties is an important factor in the design of machinery and the scaling of post-harvest operations. The present study evaluates the influence of the level of roasting and the size of grinding on the physical properties of coffee during storage. The following physical properties were evaluated: true and bulk density, and intergranular porosity. Raw coffee beans (Coffea canephora and Coffea arabica), hulled and dried, were roasted to two different levels: medium light (SCAA#65) and moderately dark (SCAA#45). The beans were then grinded into three different sizes: fine (0.59 mm), medium (0.84 mm) and coarse (1.19 mm). An additional coffee lot was kept whole. Following grinding, samples were stored at two different temperatures (10 and 30 ºC) and analyzed after five different storage durations (0, 30, 60, 120 and 180 days). The medium light roast had higher values for each of the measured physical properties. Finely ground samples had higher true and bulk densities, and porosities. It is concluded that the size of grinding, level of roasting and duration of storage significantly affect the physical properties of coffee.A determinação das propriedades físicas é fator importante na formulação de projetos de maquinários e dimensionamento de operações pós-colheita. De forma a permitir o dimensionamento correto e o uso desses maquinários, objetivou-se avaliar e determinar, durante o armazenamento, as propriedades físicas: massa específica unitária e aparente e porosidade intergranular, além de avaliar a influência dos níveis de torrefação e moagem sobre essas propriedades. Grãos de café cru (Coffea canephora e Coffea arabica) foram utilizados, descascados e secados e só então torrados em dois níveis: média clara (SCAA#65) e moderadamente escura (SCAA#45). Os grãos foram moídos em três granulometrias: fina (0,59 mm), média (0,84 mm) e grossa (1,19 mm), além do lote de café inteiro. Realizada a moagem as amostras foram armazenadas em duas temperaturas (10 e 30 ºC) e analisadas em cinco tempos distintos de armazenamento (0, 30, 60, 120 e 180 dias). A torra média clara permitiu maiores valores das propriedades físicas; já as amostras de granulometria fina apresentaram aumento das massas específica unitária e aparente e porosidade. Conclui-se que a granulometria, o nível de torrefação e o tempo de armazenamento, afetaram as propriedades físicas do café.National Council for Scientificand Technological Development/[CNPq nº 14/2012]/CNPq/BrasilUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Centro para Investigaciones en Granos y Semillas (CIGRAS