How to find the direction and sign (activation or inhibition regulation) of interaction between two genes?

11 November 2019 5 8K Report

I have a set of genes which I fed to genemania.org too that gave me possible interaction edges between genes. Lets say one such pair is PTPRD-FRMD4A. What is the best way to know about the interaction sign i.e. if PTPRD activates/inhibits FRMD4A or vice versa? Currently I am going through geneCards for GO- Biological process/molecular function understanding, to estimate the interaction sign. I am also doing correlation analysis between the two genes to estimate the type of interaction. Suppose positive correlation, then interaction wll mostly be that of activation, again negative correlation might indicate an inhbitory relation.

Is there any better way to know the direction and sign of interaction?

Thank you.

Garima Ayachit

I think you can search for signed interactions using WGCNA R package. I believe Genemania gives you a coexpression network.

https://horvath.genetics.ucla.edu/html/CoexpressionNetwork/Rpackages/WGCNA/

Read this before

https://peterlangfelder.com/2018/11/25/signed-or-unsigned-which-network-type-is-preferable/

Subhasree Majumder

Thank you for the answer. yes, Genemania does provide coexpression network but it also provided genetic interaction network on which I am currently working. correlation sign between a pair of genes can indeed give some idea about their activatory or inhibitory role in the relationship but is there some other database that lists down the activatory/inhibitory relationship between pair of genes?

Garima Ayachit

There are scattered databases based on specific diseases as you cannot have same gene expression throughout. But you could try

http://www.coexpedia.org/search.php

http://seek.princeton.edu/

Yuan-Bo Pan

The relationship (activation or inhibition) between two genes can be judged by co-expression, positive correlation means that the two genes may be activation relationship, and negative correlations are opposite.

As for judging the direction of interaction, I understand that you want to know which gene is upstream and which one is downstream. I have a few ideas to give you a reference.

You can performed WGCNA with hundreds and thousands genes (include the two gene you interested), and see the number of neighbors the two gene have. Generally, the upstream one has more neighbors and the downstream one has less neighbors.

STRING database (Protein protein interaction) http://www.string-db.org/cgi/input.pl?sessionId=oqX63tSLaISB&input_page_show_search=on

Known localization and function of the two genes. For example, the membrane proteins are often upstream genes.

You can see this paper "Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease, Cell 153, 707–720, April 25, 2013", which constructed the causal network structure.

Experimental validation

With regards

How can I integrate a routing protocol in a tiny device (e.g. Raspberry Pi)?

Timeout error!! Processor in the loop (PIL) using STM32F4 Matlab 2018a?

Could you please recommend some good journal that accept very long revie papers (approximately 6000+ words) in neurosurgery, cancer biology ?

Is it possible for two human neuronal cell lines to have different gene sequence for the same protein?

Genome-wide gene identification protocol ?

What is the difference between genotype and haplotype data in the ped format?

Any specific pipeline or parameter to analyse total transcriptomics study of brain tissue samples?

What are the patterns of human behavior that lead to COVID-19 infections?

RNA-seq DEGs downstream analysis and reporting in literature?

Could you please suggests a tutorial or paper or any other materials to learn multiple gene expression in TCGA and GTEx databases?