Table of Contents
GeneMANIA searches many large, publicly available biological datasets to find related genes. These include protein-protein, protein-DNA and genetic interactions, pathways, reactions, gene and protein expression data, protein domains and phenotypic screening profiles. Data is regularly updated.
Networks names describe the data source and are either generated from the PubMed entry associated with the data source (first author-last author-year), or simply the name of the data source (BioGRID, PathwayCommons-(original data source), Pfam)
The upload network button can be found in the advanced options panel. Your network must be for one of the GeneMANIA supported organisms, be tab delimited text, and in the format
GeneID <tab> GeneID <tab> Score. The score will vary depending on the type of network, but in general is a number ranging from zero (no interaction) to 1 (strong interaction). For an interaction network or a pathway where interactions either exist or don’t exist, the score is 1 for all links. For a gene expression network, the score could be the Pearson correlation coefficient for the gene pair, representing the expression level simiarity across several experiments.
For a co-expression network, the score could be the Pearson correlation coefficient between the expression profiles of the two genes. Note that networks are normalized to reduce the effect of highly connected nodes, so scores may change slightly once uploaded.
GeneMANIA can use a few different methods to weight networks when combining all networks to form the final composite network that results from a search. The default settings are usually appropriate, but you can choose a weighting method in the advanced option panel.
These weighting methods are based on GO terms that have between 3 and 300 genes associated with them. Only the most reliable annotations were used (i.e. all annotations with an IEA evidence code were removed, as these are less reliable). There is one weighting method per GO branch.
Each network data source is represented as a weighted interaction network where each pair of genes is assigned an association weight, which is either zero indicating no interaction, or a positive value that reflects the strength of interaction or the reliability the observation that they interact. For example, the association of a pair of genes in a gene expression dataset is the Pearson correlation coefficient of their expression levels across multiple conditions in an experiment. The more the genes are co-expressed, the higher the weight they are linked by, ranging up to 1.0, meaning perfectly correlated expression.
Direct interactions are used for networks where binary information is available (like protein interactions). When two proteins interact, their network link has a weight of 1.
Shared neighbours were used for networks where the profile of one gene was compared to that of a second gene and the Pearson correlation coefficient was calculated (like protein domain data).
The GeneMANIA database consists of genomics and proteomics data from a variety of sources, including data from gene and protein expression profiling studies and primary and curated molecular interaction networks and pathways. GeneMANIA relies on the following data sources:
The complete list of networks currently in the GeneMANIA system is available in the advanced options of the GeneMANIA query interface (click the ellipsis – “…” – in the search bar).
The Functions tab of the GeneMANIA results page displays Gene Ontology (GO) terms enriched among the genes in the network displayed by GeneMANIA.
We only consider annotations (direct or up-propagated) in GO terms with between 10 and 300 non-“IEA” and non-“RCA” annotations in the organism of interest. The GO categories and Q-values from a FDR corrected hypergeometric test for enrichment are reported, along with coverage ratios for the number of annotated genes in the displayed network vs the number of genes with that annotation in the genome. We estimate Q-values using the Benjamini-Hochberg procedure. Categories are displayed up to a Q-value cutoff of 0.1
We test for enrichment using as the foreground set all the genes in either the query list or the related genes discovered by GeneMANIA that have at least one GO annotation and as the background set all genes with GO annotations and at least one interaction in our network database.
Since the functional enrichment is computed on the displayed network, the value selected for number of related genes in the GeneMANIA advanced option’s panel will influence the results. It may be informative to try other values for this parameter, particularly if the set of functional categories is empty or small for the default value. If you only want to test the query list for enrichment, select “0” for the number of returned genes.
Web browser: GeneMANIA supports the latest versions of Chrome, Firefox, Safari and Edge. For a faster, smoother experience with GeneMANIA, we recommend you use a standards compliant browser, such as Chrome or Firefox.
Internet Connection: A fast internet connection such as DSL, Cable or T1.
Computer: A modern computer with at least a 1GHz CPU, 1GB RAM and a modern video card.
The linking URL in its simplest form is
http://genemania.org/link?o=<tid>&g=<genes>, or alternatively
<organism>: organism name or common name (e.g.
homo_sapiens) without punctuation (e.g.
<tid>: NCBI taxonomy id for organism (A. thaliana=3702, C. elegans=6239, D. melanogaster=7227, H. sapiens=9606, M. musculus=10090, S. cerevisiae=4932)
||”) – n.b. pipes must be URL-encoded as “%7C” (e.g. “pcna%7Crad51” for “pcna||rad51”)|
Examples of the simplest form:
GeneMANIA linking supports some optional parameters (reference GeneMANIA help section on meaning of the various weighting methods):
m: network combining method; must be one of the following:
automatic_relevance: Assigned based on query genes
automatic: Automatically selected weighting method
bp: biological process based
mf: molecular function based
cc: cellular component based
average: Equal by data type
average_category: Equal by network
r: the number of results generated by GeneMANIA; must be a number in the range 1..100.
If no optional parameters are provided, GeneMANIA assumes the default values:
Examples using optional parameters:
The following query runs the GeneMANIA algorithm for A. thaliana using 6 genes as input, the “average” method and returns 50 more genes:
The following query runs the GeneMANIA algorithm for A. thaliana’s CIP1 gene using the “molecular process based” method and returns 101 genes:
http://genemania.org/link?o=3702: at least one gene must be specified
http://genemania.org/link?o=1000: invalid taxonomy id
http://genemania.org/link?o=3702&g=PHYA&m=super_smart&R=50: invalid method
http://genemania.org/link?o=3702&g=det1&r=1000: results must be less than 100