DAVID bioinformatics resources consists of an integrated biological knowledgebase and analytic tools aimed at systematically extracting biological meaning from large gene/protein lists. This protocol explains how to use DAVID, a high-throughput and integrated data-mining environment, to analyze gene lists derived from high-throughput genomic experiments. The procedure first requires uploading a gene list containing any number of common gene identifiers followed by analysis using one or more text and pathway-mining tools such as gene functional classification, functional annotation chart or clustering and functional annotation table. By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.

http://dmrocke.ucdavis.edu/Class/BST226.2014.Winter/Nature%20Protocols%20DAVID.pdf

Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Functional analysis of large gene lists, derived in most cases from emerging high-throughput genomic, proteomic and bioinformatics scanning approaches, is still a challenging and daunting task. The gene-annotation enrichment analysis is a promising high-throughput strategy that increases the likelihood for investigators to identify biological processes most pertinent to their study. Approximately 68 bioinformatics enrichment tools that are currently available in the community are collected in this survey. Tools are uniquely categorized into three major classes, according to their underlying enrichment algorithms. The comprehensive collections, unique tool classifications and associated questions/issues will provide a more comprehensive and up-to-date view regarding the advantages, pitfalls and recent trends in a simpler tool-class level rather than by a tool-by-tool approach. Thus, the survey will help tool designers/developers and experienced end users understand the underlying algorithms and pertinent details of particular tool categories/tools, enabling them to make the best choices for their particular research interests.

/pdf/bioinformatics-enrichment-tools-paths-toward-the-2yo1xl3r2j.pdf

Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.

/pdf/exploring-the-full-spectrum-of-macrophage-activation-b5rnrcgcen.pdf

Exploring the full spectrum of macrophage activation.

Parasitic worms that infect people and animals cover an enormous phylogenetic spectrum within the animal kingdom. The infective larvae migrate into the nearby lymphatics and take up residence, where they mature, mate, and produce microfilaria that circulate in the bloodstream. Eggs that lodge in the tissues, particularly the liver, gut, and bladder wall, are the main cause of pathology. In the context of helminth infection, macrophages will be exposed to many signals beyond IL-4 and IL-13 that may modulate or enhance the alternatively activated phenotype. The role of macrophages in granuloma formation and control not only is important in the consideration of parasite containment, but also is one of the most important processes associated with the pathology of helminth infection. The study of macrophages in wound healing has implications far beyond helminth infection, including tissue remodeling associated with asthma and pulmonary fibrosis. Thus, although macrophages during helminth infection are actively recruited in an inflammatory context, the nature of this inflammation differs from that seen during classical macrophage activation by microbial products and IFN-γ. The induction of arginase by IL-4/IL-13 will reduce NO levels, thus acting to reduce one of the main mediators of "classical inflammation". Consistent with their roles as immune regulators, macrophages recruited to helminth infection produce high levels of the downregulatory cytokines IL-10 and TGF-β. More radically, the authors have begun to appreciate that macrophages in helminth infection have major roles in wound healing, with implications for the understanding of the evolution of Th2 immunity.

Macrophages in Helminth Infection: Effectors, Regulators, and Wound Healers

Physiologic and Pathologic Analysis of a Murine Model of Schistosomiasis Pulmonary Vascular Remodeling.

Background Fibroblasts play a key role in stricture formation in Crohn’s disease (CD) but understanding it’s pathogenesis requires a systems-level investigation to uncover new treatment targets. We studied full thickness CD tissues to characterize fibroblast heterogeneity and function by generating the first single cell RNA sequencing (scRNAseq) atlas of strictured bowel and providing proof of principle for therapeutic target validation. Methods We performed scRNAseq of 13 fresh full thickness CD resections containing non-involved, inflamed non-strictured, and strictured segments as well as 7 normal non-CD bowel segments. Each segment was separated into mucosa/submucosa or muscularis propria and analyzed separately for a total of 99 tissue samples and 409,001 cells. We validated cadherin-11 (CDH11) as a potential therapeutic target by using whole tissues, isolated intestinal cells, NanoString nCounter, next generation sequencing, proteomics and animal models. Results Our integrated dataset revealed fibroblast heterogeneity in strictured CD with the majority of stricture-selective changes detected in the mucosa/submucosa, but not the muscle layer. Cell-cell interaction modeling revealed CXCL14+ as well as MMP/WNT5A+ fibroblasts displaying a central signaling role in CD strictures. CDH11, a fibroblast cell-cell adhesion molecule, was broadly expressed and upregulated, and its pro-fibrotic function was validated by NanoString nCounter, RNA sequencing, tissue target expression, in vitro gain- and loss-of-function experiments, proteomics, and two animal models of experimental colitis. Conclusion A full-thickness bowel scRNAseq atlas revealed previously unrecognized fibroblast heterogeneity and interactions in CD strictures and CDH11 was validated as a potential therapeutic target. These results provide a new resource for a better understanding of CD stricture formation and opens potential therapeutic developments.

/pdf/stricturing-crohns-disease-single-cell-rna-sequencing-2nztwh9o.pdf

Thomas A. Wynn

Papers

Macrophages in Helminth Infection: Effectors, Regulators, and Wound Healers

Physiologic and Pathologic Analysis of a Murine Model of Schistosomiasis Pulmonary Vascular Remodeling.

Stricturing Crohn’s disease single-cell RNA sequencing reveals fibroblast heterogeneity and intercellular interactions

Immunity to the enteric nematode Trichuris muris is dependent on the Muc5ac mucin

2 Suggest Opposite Effects on Allergic α and sIL-13R α Function of Soluble (s)IL-4R Differences in Expression, Affinity, and