A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.

/pdf/the-human-microbiome-project-1armeyuv2c.pdf

The human microbiome project.

System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes/proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries. While many enrichment analysis tools and gene-set libraries databases have been developed, there is still room for improvement. Here, we present Enrichr, an integrative web-based and mobile software application that includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. We applied Enrichr to analyze nine cancer cell lines by comparing their enrichment signatures to the enrichment signatures of matched normal tissues. We observed a common pattern of up regulation of the polycomb group PRC2 and enrichment for the histone mark H3K27me3 in many cancer cell lines, as well as alterations in Toll-like receptor and interlukin signaling in K562 cells when compared with normal myeloid CD33+ cells. Such analyses provide global visualization of critical differences between normal tissues and cancer cell lines but can be applied to many other scenarios. Enrichr is an easy to use intuitive enrichment analysis web-based tool providing various types of visualization summaries of collective functions of gene lists. Enrichr is open source and freely available online at: http://amp.pharm.mssm.edu/Enrichr
 .

/pdf/enrichr-interactive-and-collaborative-html5-gene-list-1dn7g68rn1.pdf

Enrichr: Interactive and collaborative HTML5 gene list enrichment analysis tool

The Human Metabolome Database (HMDB) (www.hmdb.ca) is a resource dedicated to providing scientists with the most current and comprehensive coverage of the human metabolome. Since its first release in 2007, the HMDB has been used to facilitate research for nearly 1000 published studies in metabolomics, clinical biochemistry and systems biology. The most recent release of HMDB (version 3.0) has been significantly expanded and enhanced over the 2009 release (version 2.0). In particular, the number of annotated metabolite entries has grown from 6500 to more than 40,000 (a 600% increase). This enormous expansion is a result of the inclusion of both 'detected' metabolites (those with measured concentrations or experimental confirmation of their existence) and 'expected' metabolites (those for which biochemical pathways are known or human intake/exposure is frequent but the compound has yet to be detected in the body). The latest release also has greatly increased the number of metabolites with biofluid or tissue concentration data, the number of compounds with reference spectra and the number of data fields per entry. In addition to this expansion in data quantity, new database visualization tools and new data content have been added or enhanced. These include better spectral viewing tools, more powerful chemical substructure searches, an improved chemical taxonomy and better, more interactive pathway maps. This article describes these enhancements to the HMDB, which was previously featured in the 2009 NAR Database Issue. (Note to referees, HMDB 3.0 will go live on 18 September 2012.).

/pdf/hmdb-3-0-the-human-metabolome-database-in-2013-4rc6dnwgxh.pdf

HMDB 3.0—The Human Metabolome Database in 2013

The Human Metabolome Database or HMDB (www.hmdb.ca) is a web-enabled metabolomic database containing comprehensive information about human metabolites along with their biological roles, physiological concentrations, disease associations, chemical reactions, metabolic pathways, and reference spectra. First described in 2007, the HMDB is now considered the standard metabolomic resource for human metabolic studies. Over the past decade the HMDB has continued to grow and evolve in response to emerging needs for metabolomics researchers and continuing changes in web standards. This year's update, HMDB 4.0, represents the most significant upgrade to the database in its history. For instance, the number of fully annotated metabolites has increased by nearly threefold, the number of experimental spectra has grown by almost fourfold and the number of illustrated metabolic pathways has grown by a factor of almost 60. Significant improvements have also been made to the HMDB's chemical taxonomy, chemical ontology, spectral viewing, and spectral/text searching tools. A great deal of brand new data has also been added to HMDB 4.0. This includes large quantities of predicted MS/MS and GC-MS reference spectral data as well as predicted (physiologically feasible) metabolite structures to facilitate novel metabolite identification. Additional information on metabolite-SNP interactions and the influence of drugs on metabolite levels (pharmacometabolomics) has also been added. Many other important improvements in the content, the interface, and the performance of the HMDB website have been made and these should greatly enhance its ease of use and its potential applications in nutrition, biochemistry, clinical chemistry, clinical genetics, medicine, and metabolomics science.

https://hal.archives-ouvertes.fr/hal-01712873/document

HMDB 4.0: the human metabolome database for 2018.

DrugBank is a richly annotated resource that combines detailed drug data with comprehensive drug target and drug action information. Since its first release in 2006, DrugBank has been widely used to facilitate in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical education. The latest version of DrugBank (release 2.0) has been expanded significantly over the previous release. With approximately 4900 drug entries, it now contains 60% more FDA-approved small molecule and biotech drugs including 10% more 'experimental' drugs. Significantly, more protein target data has also been added to the database, with the latest version of DrugBank containing three times as many non-redundant protein or drug target sequences as before (1565 versus 524). Each DrugCard entry now contains more than 100 data fields with half of the information being devoted to drug/chemical data and the other half devoted to pharmacological, pharmacogenomic and molecular biological data. A number of new data fields, including food-drug interactions, drug-drug interactions and experimental ADME data have been added in response to numerous user requests. DrugBank has also significantly improved the power and simplicity of its structure query and text query searches. DrugBank is available at http://www.drugbank.ca.

/pdf/drugbank-a-knowledgebase-for-drugs-drug-actions-and-drug-h5bxks5u8l.pdf

DrugBank: a knowledgebase for drugs, drug actions and drug targets

The Human Metabolome Database (HMDB) is currently the most complete and comprehensive curated collection of human metabolite and human metabolism data in the world. It contains records for more than 2180 endogenous metabolites with information gathered from thousands of books, journal articles and electronic databases. In addition to its comprehensive literature-derived data, the HMDB also contains an extensive collection of experimental metabolite concentration data compiled from hundreds of mass spectra (MS) and Nuclear Magnetic resonance (NMR) metabolomic analyses performed on urine, blood and cerebrospinal fluid samples. This is further supplemented with thousands of NMR and MS spectra collected on purified, reference metabolites. Each metabolite entry in the HMDB contains an average of 90 separate data fields including a comprehensive compound description, names and synonyms, structural information, physico-chemical data, reference NMR and MS spectra, biofluid concentrations, disease associations, pathway information, enzyme data, gene sequence data, SNP and mutation data as well as extensive links to images, references and other public databases. Extensive searching, relational querying and data browsing tools are also provided. The HMDB is designed to address the broad needs of biochemists, clinical chemists, physicians, medical geneticists, nutritionists and members of the metabolomics community. The HMDB is available at: www.hmdb.ca

/pdf/hmdb-the-human-metabolome-database-2d337dac12.pdf

HMDB: The human metabolome database

We introduce our research on learning browsing behavior models for inferring a user's information need (corresponding to a set of words) based on the actions he has taken during his current web session This information is then used to find relevant pages, from essentially anywhere on the web The models, learned from over one hundred users during a fiveweek user study, are session-specific but independent of both the user and website Our empirical results suggest that these models can identify and satisfy the current information needs of users, even if they browse previously unseen pages containing unfamiliar words

/pdf/using-learned-browsing-behavior-models-to-recommend-relevant-uwdkfwcdt4.pdf

Using learned browsing behavior models to recommend relevant web pages

Behavior-Based Recommender Systems for Web Content : Workshop on the Next Stage of Recommender Systems Research (Beyond Personalization 2005)

This paper proposes a novel method for assessing the performance of any Web recommendation function (i.e., user model), M, used in a Web recommender sytem, based on an off-line computation using labeled session data. Each labeled session consists of a sequence of Web pages followed by a page p (IC) that contains information the user claims is relevant. We then apply M to produce a corresponding suggested page p (S) . In general, we say that M is good if p (S) has content similar to the associated p (IC) , based on the the same session. This paper defines a number of functions for estimating this p (S) to p (IC) similarity that can be used to evaluate any new models off-line, and provides empirical data to demonstrate that evaluations based on these similarity functions match our intuitions.

Off-line evaluation of recommendation functions

This paper introduces a novel method to find Web pages that satisfy the user’s current information need. The method infers the user’s need from the content of the pages the user has visited and the actions the user has applied to these pages. Unlike content-based systems that attempt to learn a user’s long-term interests, our system learns user-independent patterns of behavior that identify the user’s current information need, based on his/her current browsing session, then uses this information to suggest specific pages intended to address this need. Our system learns these behavior patterns from labeled data collected during a five-week user study, involving over one hundred participants working on their day-to-day tasks. We tested this learned model in a second phase of this same study, and found that this model can effectively identify the information needs of new users as they browse previously unseen pages, and that we can use this information to help them find relevant pages.

/pdf/goal-directed-site-independent-recommendations-from-passive-37z7qufk13.pdf

Kevin Jewell

Papers

HMDB: The human metabolome database

Using learned browsing behavior models to recommend relevant web pages

Behavior-Based Recommender Systems for Web Content : Workshop on the Next Stage of Recommender Systems Research (Beyond Personalization 2005)

Off-line evaluation of recommendation functions

Goal-directed site-independent recommendations from passive observations