THE SYNTHSEQ APPROACH TO PERSONAL GENOTYPING

Inspired by the Archon X Prize for Genomics, our research project involves implementing a novel strategy for sequencing the human genome. This prize worth $10 million will be awarded to the first company to sequence 100 human genomes with 99.999$10,000 each. However, the possibility of winning the X Prize is secondary to the prospect of revolutionizing medical diagnostics. Currently, the genomic state of‐the‐art involves identifying SNPs (single nucleotide polymorphisms) that are correlated to certain diseases. Compared to such existing diagnostics, the genome‐wide, sequence‐based biomarkers that will be made possible by fast and affordable human genome sequencing are staggering. After six months of thorough investigation and development, we are pleased to present SynthSeq, a cutting‐edge, whole‐genome sequencing venture based on the novel sequencing‐bysynthesis technology. In contrast to high‐priced competitors, our inexpensive and comparatively error‐free whole genome sequencing solution will prove to be an invaluable diagnostic resource, and it will only become more valuable as advances are made in the field of molecular diagnostics. At our intended retail price of $5,000, series A investors can expect a worst‐case MIRR of 22$700 thousand. We are confident that our innovative SynthSeq technology will deliver high‐fidelity, low‐cost whole genome sequencing to as many as 3,000 customers per year as currently envisioned, with the potential for scale‐up to millions

Plasticity in the Human Gut Microbiome Defies Evolutionary Constraints

The gut microbiome of primates, including humans, is reported to closely follow host evolutionary history, with gut microbiome composition being specific to the genetic background of its primate host. However, the comparative models used to date have mainly included a limited set of closely related primates. To further understand the forces that shape the primate gut microbiome, with reference to human populations, we expanded the comparative analysis of variation among gut microbiome compositions and their primate hosts, including 9 different primate species and 4 human groups characterized by a diverse set of subsistence patterns (n = 448 samples). The results show that the taxonomic composition of the human gut microbiome, at the genus level, exhibits increased compositional plasticity. Specifically, we show unexpected similarities between African Old World monkeys that rely on eclectic foraging and human populations engaging in nonindustrial subsistence patterns; these similarities transcend host phylogenetic constraints. Thus, instead of following evolutionary trends that would make their microbiomes more similar to that of conspecifics or more phylogenetically similar apes, gut microbiome composition in humans from nonindustrial populations resembles that of generalist cercopithecine monkeys. We also document that wild cercopithecine monkeys with eclectic diets and humans following nonindustrial subsistence patterns harbor high gut microbiome diversity that is not only higher than that seen in humans engaging in industrialized lifestyles but also higher compared to wild primates that typically consume fiber-rich diets

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Childhood environment and mental wellbeing at age 60-64 years: prospective evidence from the MRC National Survey for Health and Development:Prospective Evidence from the MRC National Survey of Health and Development

BackgroundMental wellbeing, conceptualised as positive affect, life satisfaction and realisation of needs that contribute to psychological growth, captures more than the absence of mental ill health. Several nations now aim to monitor and improve mental wellbeing. Whilst many studies document associations between adverse childhood experiences and mental disorders in adulthood, possible links between childhood experiences and adult mental wellbeing have so far received less attention.MethodsUsing data from 1976 men and women in the MRC National Survey for Health and Development, we investigated prospective associations between childhood socioeconomic and psychosocial environments and the Warwick Edinburgh Mental Wellbeing Scale, designed to capture both hedonic and eudaimonic facets of wellbeing, at age 60-64.ResultsWhilst there was no evidence that childhood socioeconomic circumstances were related to later wellbeing independently of other childhood experiences, elements of childrearing and parenting, parental health and adjustment, and childhood illness were related. More advantaged socioeconomic position was associated with greater wellbeing but this did not explain the links between these childhood exposures and adult wellbeing, suggesting alternative explanatory pathways should be considered.ConclusionsChildhood illness and family psychosocial environment are associated with mental wellbeing in early older age, with effects sizes that are larger or comparable to socioeconomic circumstances in adulthood. Initiatives to improve the nation’s mental wellbeing that include programmes targeted to supporting families and children may additionally have benefits that continue into older age

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Determination of quantum numbers for several excited charmed mesons observed in B- -> D*(+)pi(-) pi(-) decays

A four-body amplitude analysis of the B − → D * + π − π − decay is performed, where fractions and relative phases of the various resonances contributing to the decay are measured. Several quasi-model-independent analyses are performed aimed at searching for the presence of new states and establishing the quantum numbers of previously observed charmed meson resonances. In particular the resonance parameters and quantum numbers are determined for the D 1 ( 2420 ) , D 1 ( 2430 ) , D 0 ( 2550 ) , D ∗ 1 ( 2600 ) , D 2 ( 2740 ) and D ∗ 3 ( 2750 ) states. The mixing between the D 1 ( 2420 ) and D 1 ( 2430 ) resonances is studied and the mixing parameters are measured. The dataset corresponds to an integrated luminosity of 4.7     fb − 1 , collected in proton-proton collisions at center-of-mass energies of 7, 8 and 13 TeV with the LHCb detector