A framework for variation discovery and genotyping using next-generation DNA sequencing data

Recent advances in sequencing technology make it possible to comprehensively catalog genetic variation in population samples, creating a foundation for understanding human disease, ancestry and evolution. The amounts of raw data produced are prodigious, and many computational steps are required to translate this output into high-quality variant calls. We present a unified analytic framework to discover and genotype variation among multiple samples simultaneously that achieves sensitive and specific results across five sequencing technologies and three distinct, canonical experimental designs. Our process includes (i) initial read mapping; (ii) local realignment around indels; (iii) base quality score recalibration; (iv) SNP discovery and genotyping to find all potential variants; and (v) machine learning to separate true segregating variation from machine artifacts common to next-generation sequencing technologies. We here discuss the application of these tools, instantiated in the Genome Analysis Toolkit, to deep whole-genome, whole-exome capture and multi-sample low-pass (～4×) 1000 Genomes Project datasets.     

Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells

At sites of inflammation and tumor growth, the local concentration of extracellular adenosine rapidly increases and plays a role in controlling the immune responses of nearby cells. Adenosine deaminases ADA1 and ADA2 (ADAs) decrease the level of adenosine by converting it to inosine, which serves as a negative feedback mechanism. Mutations in the genes encoding ADAs lead to impaired immune function, which suggests a crucial role for ADAs in immune system regulation. It is not clear why humans and other mammals possess two enzymes with adenosine deaminase activity. Here, we found that ADA2 binds to neutrophils, monocytes, NK cells and B cells that do not express CD26, a receptor for ADA1. Moreover, the analysis of CD4+ T-cell subset revealed that ADA2 specifically binds to regulatory T cells expressing CD39 and lacking the receptor for ADA1. Also, it was found that ADA1 binds to CD16? monocytes, while CD16+ monocytes preferably bind ADA2. A study of the blood samples from ADA2-deficient patients showed a dramatic reduction in the number of lymphocyte subsets and an increased concentration of TNF-α in plasma. Our results suggest the existence of a new mechanism, where the activation and survival of immune cells is regulated through the activities of ADA2 or ADA1 anchored to the cell surface.     

Revision of the genus Delopleurus Boheman (Coleoptera: Scarabaeidae: Scarabaeinae) with description of new species from Africa

The genus Delopleurus Erichson, 1847, is revised. Five new species are described from Africa: Delopleurus naviauxi sp. nov., Delopleurus krikkeni sp. nov., Delopleurus darrenmanni sp. nov., Delopleurus fossatus sp. nov. and Delopleurus pubescens sp. nov. One new synonymy is established (Delopleurus parvus (Sharp, 1875) = Delopleurus cardoni Paulian, 1934, syn. nov.). Lectotype of Delopleurus pullus Boheman, 1857, is designated. Delopleurus janssensi Frey, 1963, is transferred to the genus Metacatharsius Paulian, 1939. A key to the Delopleurus species and locality maps are given.

http://zoobank.org/urn:lsid:zoobank.org:pub:67AE5CC5-9C9C-4872-A2B6-68C3BA82C44A     

Composition,characteristics and long-term variability of the freshwater microcrustacean fauna of the Faroe Islands

ABSTRACT

Despite the accessibility of the Faroe Islands, faunistic research on their numerous lakes and ponds is quite rare. The biota of Faroese freshwaters is still underexplored, and its specific traits raise many questions. In the present survey, 32 microcrustacean species were observed, 8 of which were new to the Faroese fauna. The obtained species list shows that Cladocera species prevail over Copepoda here, which is not typical of northern territories. This fact is due to (1) the extraordinarily warm climate of the Faroe Islands compared to other areas at similar latitudes because of the heating effect of the surrounding North Atlantic Current and (2) the lack of calanoid species, which have never been found in the freshwaters of the Faroe Islands. The diachronic analysis of the species diversity and composition over the centuries of research on the archipelago showed no evidence of the impact of global climate change on the fauna.     

Human gut microbiome viewed across age and geography

Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.     

Nonlinear identification of judgmental forecasts effects at SKU level

Prediction of demand is a key component within supply chain management. Improved accuracy in forecasts directly affects all levels of the supply chain, reducing stock costs and increasing customer satisfaction. In many application areas, demand prediction relies on statistical software which provides an initial forecast subsequently modified by the expert's judgment. This paper outlines a new methodology based on state‐dependent parameter (SDP) estimation techniques to identify the nonlinear behaviour of such managerial adjustments. This non‐parametric SDP estimate is used as a guideline to propose a nonlinear model that corrects the bias introduced by the managerial adjustments. One‐step‐ahead forecasts of stock‐keeping unit sales sampled monthly from a manufacturing company are utilized to test the proposed methodology. The results indicate that adjustments introduce a nonlinear pattern, undermining accuracy. This understanding can be used to enhance the design of the forecasting support system in order to help forecasters towards more efficient judgmental adjustments. Copyright © 2010 John Wiley & Sons, Ltd.     

Zenkevitchiidae fam. nov. (Crustacea: Gammaroidea), with description of new subterranean amphipods from extremely deep cave habitats

Previous phylogenetic analysis based on combined mitochondrial and nuclear gene sequences detected paraphyly of the Typhlogammaridae. To test this hypothesis a portion of large subunit (LSU-rDNA) gene sequences were obtained for typhlogammarid species from Caucasus. The Bayesian approach to LSU-rDNA sequences provided evidence for an independent origin of the Dinaric and Caucasus ‘typhlogammarid’ clades. A new family, Zenkevitchiidae fam. nov., is proposed to reconcile the observed phylogeny with the concept of monophyly. Using light microscopy, two mouthpart morphotypes of the Zenkevitchiidae fam. nov. species with quite different setae are identified. Taking into account these two morphotypes, a new classification is proposed – Adaugammarus revazi comb. nov., and Adaugammarus sandroruffoi comb. nov. Additionally, two new stygobiont zenkevitchiid amphipod species – Adaugammarus kasiani sp. nov. and Kruberia relicta sp. nov. – are described from Krubera Cave in Abkhazia. A distribution map and an identification key for the Zenkevitchiidae fam. nov. species of Transcaucasia are provided.

http://zoobank.org/urn:lsid:zoobank.org:pub:90177B0C-BED0-4601-8CFC-3F774B22065C