Rob Knight

Bio: Rob Knight is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Microbiome & Gut flora. The author has an hindex of 201, co-authored 1061 publications receiving 253207 citations. Previous affiliations of Rob Knight include Anschutz Medical Campus & University of Sydney.

The efficacy and safety of lenalidomide plus dexamethasone in relapsed or refractory multiple myeloma patients with impaired renal function

Abstract: 8542 Background: Renal impairment (RI) is common among patients (pts) presenting with myeloma (MM) and requires aggressive early intervention. Two recently published phase III trials showed significant benefit after treatment with lenalidomide plus dexamethasone (Len/Dex) over Dex alone for pts with refractory or relapsing MM. Methods: In pooled data, 682 pts with serum creatinine (Cr) ≤2.5 mg/dL received treatment at a starting dose of 25 mg/day Len on days 1–21 and 40 mg/day Dex on days 1–4, 9–12, and 17–20days 1–4, every 28-day cycle. We now evaluate efficacy and safety of Len/Dex and Dex alone in the subgroup of pts who had normal (CLcr >80 mL/min), mild (50≤ CLcr <80 mL/min), moderate (30≤ CLcr <50 mL/min), or severe (CLcr <30 mL/min) RI despite Cr ≤2.5mg/dL. Results: Len/Dex significantly improved time-to-progression and response rate compared with Dex for pts with normal to moderately impaired RI (Table; P<0.001); in severe RI TTP was significantly longer with Dex alone, but shorter than for pts wi...

Metagenomic covariation along densely sampled environmental gradients in the Red Sea

Abstract: Oceanic microbial diversity covaries with physicochemical parameters. Temperature, for example, explains approximately half of global variation in surface taxonomic abundance. It is unknown, however, whether covariation patterns hold over narrower parameter gradients and spatial scales, and extending to mesopelagic depths. We collected and sequenced 45 epipelagic and mesopelagic microbial metagenomes on a meridional transect through the eastern Red Sea. We asked which environmental parameters explain the most variation in relative abundances of taxonomic groups, gene ortholog groups, and pathways -- at a spatial scale of <2000 km, along narrow but well-defined latitudinal and depth-dependent gradients. We also asked how microbes are adapted to gradients and extremes in irradiance, temperature, salinity, and nutrients, examining the responses of individual gene ortholog groups to these parameters. Functional and taxonomic metrics were equally well explained (75-79%) by environmental parameters. However, only functional and not taxonomic covariation patterns were conserved when comparing with an intruding water mass with different physicochemical properties. Temperature explained the most variation in each metric, followed by nitrate, chlorophyll, phosphate, and salinity. That nitrate explained more variation than phosphate suggested nitrogen limitation, consistent with low surface N:P ratios. Covariation of gene ortholog groups with environmental parameters revealed patterns of functional adaptation to the challenging Red Sea environment: high irradiance, temperature, salinity, and low nutrients. Nutrient acquisition gene ortholog groups were anticorrelated with concentrations of their respective nutrient species, recapturing trends previously observed across much larger distances and environmental gradients. This dataset of metagenomic covariation along densely sampled environmental gradients includes online data exploration supplements, serving as a community resource for marine microbial ecology.

CD8 T cells drive anorexia, dysbiosis, and blooms of a commensal with immunosuppressive potential after viral infection.

Abstract: Infections elicit immune adaptations to enable pathogen resistance and/or tolerance and are associated with compositional shifts of the intestinal microbiome. However, a comprehensive understanding of how infections with pathogens that exhibit distinct capability to spread and/or persist differentially change the microbiome, the underlying mechanisms, and the relative contribution of individual commensal species to immune cell adaptations is still lacking. Here, we discovered that mouse infection with a fast-spreading and persistent (but not a slow-spreading acute) isolate of lymphocytic choriomeningitis virus induced large-scale microbiome shifts characterized by increased Verrucomicrobia and reduced Firmicute/Bacteroidetes ratio. Remarkably, the most profound microbiome changes occurred transiently after infection with the fast-spreading persistent isolate, were uncoupled from sustained viral loads, and were instead largely caused by CD8 T cell responses and/or CD8 T cell-induced anorexia. Among the taxa enriched by infection with the fast-spreading virus, Akkermansia muciniphila, broadly regarded as a beneficial commensal, bloomed upon starvation and in a CD8 T cell-dependent manner. Strikingly, oral administration of A. muciniphila suppressed selected effector features of CD8 T cells in the context of both infections. Our findings define unique microbiome differences after chronic versus acute viral infections and identify CD8 T cell responses and downstream anorexia as driver mechanisms of microbial dysbiosis after infection with a fast-spreading virus. Our data also highlight potential context-dependent effects of probiotics and suggest a model in which changes in host behavior and downstream microbiome dysbiosis may constitute a previously unrecognized negative feedback loop that contributes to CD8 T cell adaptations after infections with fast-spreading and/or persistent pathogens.

Author Correction: Farm-like indoor microbiota in non-farm homes protects children from asthma development.

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

QIIME allows analysis of high-throughput community sequencing data.

Abstract: Supplementary Figure 1 Overview of the analysis pipeline. Supplementary Table 1 Details of conventionally raised and conventionalized mouse samples. Supplementary Discussion Expanded discussion of QIIME analyses presented in the main text; Sequencing of 16S rRNA gene amplicons; QIIME analysis notes; Expanded Figure 1 legend; Links to raw data and processed output from the runs with and without denoising.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

The SILVA ribosomal RNA gene database project: improved data processing and web-based tools

Abstract: SILVA (from Latin silva, forest, http://www.arb-silva.de) is a comprehensive web resource for up to date, quality-controlled databases of aligned ribosomal RNA (rRNA) gene sequences from the Bacteria, Archaea and Eukaryota domains and supplementary online services. The referred database release 111 (July 2012) contains 3 194 778 small subunit and 288 717 large subunit rRNA gene sequences. Since the initial description of the project, substantial new features have been introduced, including advanced quality control procedures, an improved rRNA gene aligner, online tools for probe and primer evaluation and optimized browsing, searching and downloading on the website. Furthermore, the extensively curated SILVA taxonomy and the new non-redundant SILVA datasets provide an ideal reference for high-throughput classification of data from next-generation sequencing approaches.

Introducing mothur: Open-Source, Platform-Independent, Community-Supported Software for Describing and Comparing Microbial Communities

Abstract: mothur aims to be a comprehensive software package that allows users to use a single piece of software to analyze community sequence data. It builds upon previous tools to provide a flexible and powerful software package for analyzing sequencing data. As a case study, we used mothur to trim, screen, and align sequences; calculate distances; assign sequences to operational taxonomic units; and describe the alpha and beta diversity of eight marine samples previously characterized by pyrosequencing of 16S rRNA gene fragments. This analysis of more than 222,000 sequences was completed in less than 2 h with a laptop computer.

Search and clustering orders of magnitude faster than BLAST

Abstract: Motivation: Biological sequence data is accumulating rapidly, motivating the development of improved high-throughput methods for sequence classification. Results: UBLAST and USEARCH are new algorithms enabling sensitive local and global search of large sequence databases at exceptionally high speeds. They are often orders of magnitude faster than BLAST in practical applications, though sensitivity to distant protein relationships is lower. UCLUST is a new clustering method that exploits USEARCH to assign sequences to clusters. UCLUST offers several advantages over the widely used program CD-HIT, including higher speed, lower memory use, improved sensitivity, clustering at lower identities and classification of much larger datasets. Availability: Binaries are available at no charge for non-commercial use at http://www.drive5.com/usearch Contact: [email protected] Supplementary information:Supplementary data are available at Bioinformatics online.