NutriGenomeDB: a nutrigenomics exploratory and analytical platform

Habitual consumption of certain foods has shown beneficial and protective effects against multiple chronic diseases. However, it is not clear by which molecular mechanisms they may exert their beneficial effects. Multiple -omic experiments available in public databases have generated gene expression data following the treatment of human cells with different food nutrients and bioactive compounds. Exploration of such data in an integrative manner offers excellent possibilities for gaining insights into the molecular effects of food compounds and bioactive molecules at the cellular level. Here we present NutriGenomeDB, a web-based application that hosts manually curated gene sets defined from gene expression signatures, after differential expression analysis of nutrigenomics experiments performed on human cells available in the Gene Expression Omnibus (GEO) repository. Through its web interface, users can explore gene expression data with interactive visualizations. In addition, external gene signatures can be connected with nutrigenomics gene sets using a gene pattern-matching algorithm. We further demonstrate how the application can capture the primary molecular mechanisms of a drug used to treat hypertension and thus connect its mode of action with hosted food compounds.

[1]  Guy E. Zinman,et al.  ExpressionBlast: mining large, unstructured expression databases , 2013, Nature Methods.

[2]  Kathleen M Jagodnik,et al.  Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd , 2016, Nature Communications.

[3]  J. Nielsen,et al.  Nutritional systems biology: definitions and approaches. , 2009, Annual review of nutrition.

[4]  Gareth Williams SPIEDw: a searchable platform-independent expression database web tool , 2013, BMC Genomics.

[5]  Diego di Bernardo,et al.  gene2drug: a Computational Tool for Pathway-based Rational Drug Repositioning , 2017, bioRxiv.

[6]  K. Shetty,et al.  Potential of cranberry-based herbal synergies for diabetes and hypertension management. , 2006, Asia Pacific journal of clinical nutrition.

[7]  J. Hodgson,et al.  Randomised, Controlled, Cross-Over Trial of Soy Protein with Isoflavones on Blood Pressure and Arterial Function in Hypertensive Subjects , 2006, Journal of the American College of Nutrition.

[8]  Paul A Clemons,et al.  The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease , 2006, Science.

[9]  S. Knapp,et al.  Dietary Compound Resveratrol Is a Pan-BET Bromodomain Inhibitor , 2017, Nutrients.

[10]  Anil G Jegga,et al.  Transcriptomic Data Mining and Repurposing for Computational Drug Discovery. , 2018, Methods in molecular biology.

[11]  Peter Murray-Rust,et al.  Minimum information about a bioactive entity (MIABE) , 2011, Nature Reviews Drug Discovery.

[12]  C. G. Mohan,et al.  Antiobesity and lipid lowering effects of Glycyrrhiza chalcones: experimental and computational studies. , 2011, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[13]  Gemma Vilahur,et al.  Systems biology approaches to understand the effects of nutrition and promote health. , 2017, British journal of clinical pharmacology.

[14]  R. Naviaux,et al.  Englerin A induces an acute inflammatory response and reveals lipid metabolism and ER stress as targetable vulnerabilities in renal cell carcinoma , 2017, PloS one.

[15]  Jun-yi Zeng,et al.  Genistein attenuates monocrotaline-induced pulmonary arterial hypertension in rats by activating PI3K/Akt/eNOS signaling. , 2017, Histology and histopathology.

[16]  Shuxing Zhang,et al.  Computational polypharmacology: a new paradigm for drug discovery , 2017, Expert opinion on drug discovery.

[17]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Jun Li,et al.  Designing Dietary Recommendations Using System Level Interactomics Analysis and Network-Based Inference , 2017, Front. Physiol..

[19]  Lei Wang,et al.  A Combination of Intravenous Genistein Plus Mg2+ Enhances Antihypertensive Effects in SHR by Endothelial Protection and BKCa Channel Inhibition. , 2015, American journal of hypertension.

[20]  Salil Sharma,et al.  Genistein, a Soy Phytoestrogen, Reverses Severe Pulmonary Hypertension and Prevents Right Heart Failure in Rats , 2012, Hypertension.

[21]  A. Dávalos,et al.  Data mining of nutrigenomics experiments: Identification of a cancer protective gene signature , 2018 .

[22]  Tao Jiang,et al.  NeoDTI: Neural integration of neighbor information from a heterogeneous network for discovering new drug-target interactions , 2018, bioRxiv.

[23]  H. Hosseinzadeh,et al.  Rosemary (Rosmarinus officinalis) as a potential therapeutic plant in metabolic syndrome: a review , 2016, Naunyn-Schmiedeberg's Archives of Pharmacology.

[24]  Youngmi Yoon,et al.  Drug voyager: a computational platform for exploring unintended drug action , 2017, BMC Bioinformatics.

[25]  A. Sureda,et al.  Hypotensive effects of genistein: From chemistry to medicine. , 2017, Chemico-biological interactions.

[26]  Alberto D. Pascual-Montano,et al.  NFFinder: an online bioinformatics tool for searching similar transcriptomics experiments in the context of drug repositioning , 2015, Nucleic Acids Res..

[27]  Adeeb Rahman,et al.  Clustergrammer, a web-based heatmap visualization and analysis tool for high-dimensional biological data , 2017, Scientific Data.

[28]  R. Doll,et al.  The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. , 1981, Journal of the National Cancer Institute.

[29]  W. Maldonado-Rojas,et al.  Potential interaction of natural dietary bioactive compounds with COX-2. , 2011, Journal of molecular graphics & modelling.

[30]  J. Hodgson,et al.  Effects of isoflavonoids on blood pressure in subjects with high-normal ambulatory blood pressure levels: a randomized controlled trial. , 1999, American journal of hypertension.

[31]  R. C. M. Oliveira,et al.  Pharmacological and biotechnological advances with Rosmarinus officinalis L , 2018, Expert opinion on therapeutic patents.