GenePath

Category Genomics>Genetic Data Analysis/Tools and Cross-Omics>Pathway Analysis/Gene Regulatory Networks/Tools

Abstract GenePath is a web-enabled intelligent assistant for the analysis of genetic data and for discovery of genetic networks. GenePath uses 'abductive inference' to elucidate network constraints and logic to derive consistent networks.

Typically, it starts with a set of genetic experiments, uses a set of embedded rules (Patterns - see below...) to infer relations between genes and outcome, and based on these relations constructs a genetic network.

GenePath implements a framework for reasoning about genetic experiments and hypothesizing genetic networks. This framework consists of the following entities:

1) Genetic data - i.e., experiments with mutations and corresponding outcomes;

2) Background Knowledge - in the form of known relations between genes and biological processes;

3) Expert-defined 'Reasoning Patterns' - used by GenePath to abduce gene relations from genetic experiments;

4) Abductive 'Inference Engine' - that matches the encoded patterns with genetic data to obtain constraints over the genetic network;

5) Network Synthesis - that constructs a network (hypothesis) that is consistent with genetic data, abduced constraints and background knowledge and an;

6) Engine for the proposal of Genetic Experiments - that, given existing genetic data and abduced constrains, proposes sets of additional experiments that would refine the derived network and provide evidence for relations that could Not be established from the existing data set.

Patterns --

GenePath can assist in the construction of ‘genetic pathways’ from genetic data.

It mimics the geneticist by applying a set of patterns that search for specific gene-to-gene or gene-to-biological process relations. The relations include:

1) Epistasis (two genes act in a linear pathway and one follows the other).

2) Parallel (two genes act in parallel pathways).

3) Influences (a gene influences the biological process).

4) Non-influences (a gene does Not influence the biological process).

Patterns are expressed as rules. For instance, the simplest pattern is "IF a mutation in a gene changes the phenotype relative to an otherwise identical strain THEN the gene influences the biological process" which, when applied to genetic data, may find influences relations.

Relations found by GenePath are then used as constraints over the possible genetic networks that can explain the data.

While a number of such networks may exist, GenePath proposes a single pathway that accounts for all the epistatic and influences relations.

Here is a list of patterns that are implemented in the current version of GenePath:

Relation Epistasis -

Pattern epMut: Assuming a linear pathway, IF two different mutations (of genes A and B) result in two different phenotypes AND the phenotype of the double gene mutation is the same as one of the single gene mutations (B), THEN that single gene mutation (B) is epistatic AND gene B is considered to act after gene A.

Pattern epEss: Assuming a linear pathway, IF two different mutations (of genes A and B) result in two different expression levels of another gene AND the expression of that gene in a strain with a double gene mutation is the same as one of the single gene mutations (B), THEN that single gene mutation (B) is epistatic AND gene B is considered to act after gene A.

Pattern epTC: IF gene A precedes gene B AND gene B precedes gene C THEN gene A precedes gene C. Note: this relation can be applied recursively (Transitive Closure).

Relation Parallel -

Pattern parDiff: Two genes are in parallel pathways IF mutations in either gene have an effect on the biological process AND the phenotype of the double mutant is different from the phenotype of either mutation alone.

Pattern parEss: Two genes are in parallel pathways IF mutations in either gene have an effect on some other gene AND the expression of that other gene in the double-mutant is different from either mutation alone.

Pattern parTC: IF genes A and B act in parallel pathways AND genes B and C act in parallel pathways THEN genes A and C also act in parallel pathways. (Note: this relation can be applied recursively (Transitive Closure).

Relation Influences -

Pattern inf: IF a mutation in a gene changes the phenotype relative to an otherwise identical strain THEN the gene influences the biological process.

Pattern infEss: IF a mutation in gene A changes the expression of gene B relative to an otherwise identical strain THEN gene A influences gene B.

Pattern infTC: IF gene A precedes gene B AND gene B influences the biological process THEN gene A influences the biological process. Note: this relation can be applied recursively (Transitive Closure).

Relation Non-Influences -

Pattern notInf: IF a mutation in a gene does Not change the phenotype THEN the gene does Not influence the biological process.

The manufacturer currently offers a second version of GenePath. It was developed with Microsoft ASP.NET technology, has a completely rebuilt interface, and according to the manufacturer is much faster than the previous version.

It includes a number of New features:

1) Expression data analysis;

2) Handling confidences assigned to genetic data;

3) Derivation of genetic networks with confidences computed for relations in the network;

4) Dealing with conflicts;

5) Treatment of cycles;

6) Experiment planning; and

7) Enhanced what-if analysis.

System Requirements

Web based.

Manufacturer

GenePath is a result of collaboration between the

Laboratory for Artificial Intelligence Laboratory at Faculty of Computer and Information Science, University of Ljubljana, Slovenia, and

Baylor College of Medicine, Departments of Molecular and Human Genetics and Biochemistry and Molecular Biology, Houston, TX.

Manufacturer Web Site GenePath

Price Free

G6G Abstract Number 20302

G6G Manufacturer Number 102831