This tutorial illustrates an example on how to traverse through Lynx and its functionalities.
From a biological perspective Autism Spectrum Disorders (ASD) are known to be associated with increased incidence of epilepsy. The example shows how a user can generate gene sets and relevant molecular mechanisms contributing to seizures in patients with Autism.
NOTE: The search results in the use case may differ from the actual results eventually due the updated databases or additional sources added.
Tutorial created using Jing Software on 08-20-2013.
Step 1: The user can start from Search page in Lynx from the right-side corner of the front page and search for gene sets related autism. The user can perform ‚Äòfuzzy‚Äô search for autism candidate genes against ‚Äòdisease‚Äô object. This results in 483 genes for autism from various sources such as OMIM, AutDB and disease database all integrated in Lynx Knowledgebase (Lynxkb).
Step 2: The search can be further refined for epileptic symptom related genes from the autism set. The genes can be further filtered using ‚Äòseizures‚Äô as a fuzzy search term. This results in a total of 59 genes that are shared between autism and epilepsy.
Step 3: The set of this 59 genes can then be submitted to Enrichment analysis or Network-Based Prioritization (NBP) to find relevant genes and molecular mechanisms contributing to seizures in autism.
Step 4: The enrichment page within Lynx for these set of genes showed over representation of the functional categories associated with ionotropic glutamate receptor binding, synaptic transmission and voltage-gated sodium channel all relevant categories already associated with ASD as well as epileptic phenotype.
Step 5: The user can also submit the 59 genes to Network-based Prioritization page that allows selecting high confidence genes and subnetworks relevant to user's interest.
Step 6: The query set can be either assigned a rank based on their strength of association with autism or can be assigned a flat score of '1' by default in the Network Prioritization Page. The heat-kernel ranking algorithm is used as a default algorithm with STRING 9.0 as an underlying global network for prediction. The resulting gene sets are prioritized by their P-value.
Step 7: The result set from the NBP can be again fed as an input to enrichment analysis tool. The priortized genes also show enrichment for relevant categories such as synpatic transmission, ionotropic glutamate receptor binding and voltage-gated sodium channel all molecular mechanisms again relevant to ASD with seizure phenotypes.
Step 8: The user can also download the results at every step for futher analysis.