Dataset Information

The Impact of Pathway Database Choice on Statistical Enrichment Analysis and Predictive Modeling.

ABSTRACT: Pathway-centric approaches are widely used to interpret and contextualize -omics data. However, databases contain different representations of the same biological pathway, which may lead to different results of statistical enrichment analysis and predictive models in the context of precision medicine. We have performed an in-depth benchmarking of the impact of pathway database choice on statistical enrichment analysis and predictive modeling. We analyzed five cancer datasets using three major pathway databases and developed an approach to merge several databases into a single integrative one: MPath. Our results show that equivalent pathways from different databases yield disparate results in statistical enrichment analysis. Moreover, we observed a significant dataset-dependent impact on the performance of machine learning models on different prediction tasks. In some cases, MPath significantly improved prediction performance and also reduced the variance of prediction performances. Furthermore, MPath yielded more consistent and biologically plausible results in statistical enrichment analyses. In summary, this benchmarking study demonstrates that pathway database choice can influence the results of statistical enrichment analysis and predictive modeling. Therefore, we recommend the use of multiple pathway databases or integrative ones.

SUBMITTER: Mubeen S

PROVIDER: S-EPMC6883970 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Impact of Pathway Database Choice on Statistical Enrichment Analysis and Predictive Modeling.

Mubeen Sarah S Hoyt Charles Tapley CT Gemünd André A Hofmann-Apitius Martin M Fröhlich Holger H Domingo-Fernández Daniel D

Frontiers in genetics 20191122

Pathway-centric approaches are widely used to interpret and contextualize -<i>omics</i> data. However, databases contain different representations of the same biological pathway, which may lead to different results of statistical enrichment analysis and predictive models in the context of precision medicine. We have performed an in-depth benchmarking of the impact of pathway database choice on statistical enrichment analysis and predictive modeling. We analyzed five cancer datasets using three m ...[more]

PMID: 31824580

Similar Datasets

Project description:BackgroundNext-Generation Sequencing (NGS) technologies and Genome-Wide Association Studies (GWAS) generate millions of reads and hundreds of datasets, and there is an urgent need for a better way to accurately interpret and distill such large amounts of data. Extensive pathway and network analysis allow for the discovery of highly significant pathways from a set of disease vs. healthy samples in the NGS and GWAS. Knowledge of activation of these processes will lead to elucidation of the complex biological pathways affected by drug treatment, to patient stratification studies of new and existing drug treatments, and to understanding the underlying anti-cancer drug effects. There are approximately 141 biological human pathway resources as of Jan 2012 according to the Pathguide database. However, most currently available resources do not contain disease, drug or organ specificity information such as disease-pathway, drug-pathway, and organ-pathway associations. Systematically integrating pathway, disease, drug and organ specificity together becomes increasingly crucial for understanding the interrelationships between signaling, metabolic and regulatory pathway, drug action, disease susceptibility, and organ specificity from high-throughput omics data (genomics, transcriptomics, proteomics and metabolomics).ResultsWe designed the Integrated Pathway Analysis Database for Systematic Enrichment Analysis (IPAD, http://bioinfo.hsc.unt.edu/ipad), defining inter-association between pathway, disease, drug and organ specificity, based on six criteria: 1) comprehensive pathway coverage; 2) gene/protein to pathway/disease/drug/organ association; 3) inter-association between pathway, disease, drug, and organ; 4) multiple and quantitative measurement of enrichment and inter-association; 5) assessment of enrichment and inter-association analysis with the context of the existing biological knowledge and a "gold standard" constructed from reputable and reliable sources; and 6) cross-linking of multiple available data sources.IPAD is a comprehensive database covering about 22,498 genes, 25,469 proteins, 1956 pathways, 6704 diseases, 5615 drugs, and 52 organs integrated from databases including the BioCarta, KEGG, NCI-Nature curated, Reactome, CTD, PharmGKB, DrugBank, PharmGKB, and HOMER. The database has a web-based user interface that allows users to perform enrichment analysis from genes/proteins/molecules and inter-association analysis from a pathway, disease, drug, and organ.Moreover, the quality of the database was validated with the context of the existing biological knowledge and a "gold standard" constructed from reputable and reliable sources. Two case studies were also presented to demonstrate: 1) self-validation of enrichment analysis and inter-association analysis on brain-specific markers, and 2) identification of previously undiscovered components by the enrichment analysis from a prostate cancer study.ConclusionsIPAD is a new resource for analyzing, identifying, and validating pathway, disease, drug, organ specificity and their inter-associations. The statistical method we developed for enrichment and similarity measurement and the two criteria we described for setting the threshold parameters can be extended to other enrichment applications. Enriched pathways, diseases, drugs, organs and their inter-associations can be searched, displayed, and downloaded from our online user interface. The current IPAD database can help users address a wide range of biological pathway related, disease susceptibility related, drug target related and organ specificity related questions in human disease studies.

Project description:The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be checked multiple times a year and RaMP will be updated accordingly.

Project description:This paper reports a two-part study examining the relationship between fear of missing out (FoMO) and maladaptive behaviors in college students. This project used a cross-sectional study to examine whether college student FoMO predicts maladaptive behaviors across a range of domains (e.g., alcohol and drug use, academic misconduct, illegal behavior). Participants (N = 472) completed hard copy questionnaire packets assessing trait FoMO levels and questions pertaining to unethical and illegal behavior while in college. Part 1 utilized traditional statistical analyses (i.e., hierarchical regression modeling) to identify any relationships between FoMO, demographic variables (socioeconomic status, living situation, and gender) and the behavioral outcomes of interest. Part 2 looked to quantify the predictive power of FoMO, and demographic variables used in Part 1 through the convergent approach of supervised machine learning. Results from Part 1 indicate that college student FoMO is indeed related to many diverse maladaptive behaviors spanning the legal and illegal spectrum. Part 2, using various techniques such as recursive feature elimination (RFE) and principal component analysis (PCA) and models such as logistic regression, random forest, and Support Vector Machine (SVM), showcased the predictive power of implementing machine learning. Class membership for these behaviors (offender vs. non-offender) was predicted at rates well above baseline (e.g., 50% at baseline vs 87% accuracy for academic misconduct with just three input variables). This study demonstrated FoMO's relationships with these behaviors as well as how machine learning can provide additional predictive insights that would not be possible through inferential statistical modeling approaches typically employed in psychology, and more broadly, the social sciences. Research in the social sciences stands to gain from regularly utilizing the more traditional statistical approaches in tandem with machine learning.

Dataset Information

The Impact of Pathway Database Choice on Statistical Enrichment Analysis and Predictive Modeling.

Publications

The Impact of Pathway Database Choice on Statistical Enrichment Analysis and Predictive Modeling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets