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MP-BioPath

A command line tool for modelling the effects of perterbations on biological pathways.

For a full user guide please refer to the following document

Installation

Julia (http://julialang.org/)

Linux

apt-get install julia

Dependencies

This will install all the Julia modules that the tool relies on

make install

Running Inference

./bin/pgmlab --help

Install TSNe package

First enter Julia console

julia

In Julia console install

``julia Pkg.clone("git://github.com/lejon/TSne.jl.git")

# Downloading Expression Data

Go to https://www.ebi.ac.uk/gxa/experiments/ to find the expression file you would like to use.

```bash
curl -o data/expression-data.tsv https://www.ebi.ac.uk/gxa/experiments/E-MTAB-2836.tsv?geneQuery=%5B%7B%22value%22%3A%22protein_coding%22%2C%22category%22%3A%22gene_biotype%22%7D%5D

Gene to uniprot mapping

This was created through the uniprot user interfaces. A list of Ensemble IDs, from the expression data, were provided and mapped to UniProt ids (http://www.uniprot.org/)

Results were saved to data/Expression_Atlas_ENSEMBL_gene_to_UniProt_mapping.txt

Essential Genes source

http://ogee.medgenius.info/browse/

Convert gene names to HUGO

http://useast.ensembl.org/Help/Faq?id=125

Used biomart central to download a list of HUGO gene symbols to match the ensemble geneIDs. The exact query can be found in the script "get_gene_id_mapping_from_biomart_central.pl" that was generated by Biomart Central.

Got list of unique genes with following command

grep -v "TextMining" essential_9606_all.txt | awk -F"\t" '$4 == "E" { print $3 }' | sort | uniq > essential_9606_all_gene_ids.txt

Synthetically lethal

The two files sl_human and sdl_human were downloaded from: http://histone.sce.ntu.edu.sg/SynLethDB/downloadPage.php

And more information about the data can be found in the following articles:

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445436/ "The authors also analyzed synthetic dosage lethality (SDL), which is the overexpression of a gene that leads to the essentiality of a second gene, making a SDL pair"
• http://nar.oxfordjournals.org/content/early/2015/10/29/nar.gkv1108.full

Coexpression Data

http://coxpresdb.jp/download.shtml

##Coespression DB API

http://coxpresdb.jp/help/API.shtml

Test

julia scripts/analyzeBioNetwork.jl ~/git/PGM/Pathways\ where\ negative\ OR\ is\ AND/PIP3_activates_AKT_signaling_Sept23_2016_sorted_checked_patched_1_NegativeORtoAND.txt ~/git/PGM/InputDataForTesting/Mock_Short_Input_Data_for_PIP3_Activates_AKT_Signaling_Text.txt --key-outputs
```bash

## Find SI
```bash
julia scripts/analyzeBioNetwork.jl ~/git/PGM/Pathways\ where\ negative\ OR\ is\ AND/PIP3_activates_AKT_signaling_Sept23_2016_sorted_checked_patched_1_NegativeORtoAND.txt --find-si --key-outputs

Get unique SI Pairs

cut -f2,4 PIP3_activates_AKT_signaling_Sept23_2016_sorted_checked_patched_1_NegativeORtoAND.txt.si | sort | uniq  > PIP3_activates_AKT_signaling_Sept23_2016_sorted_checked_patched_1_NegativeORtoAND.txt.si.uniq

test commands

time julia scripts/analyzeBioNetwork.jl ~/git/PGM/Pathways_where_negative_OR_is_AND/PIP3_activates_AKT_signaling_Sept23_2016_sorted_checked_patched_1_NegativeORtoAND.txt --find-si

julia scripts/analyzeBioNetwork.jl ~/git/PGM/Pathways_where_negative_OR_is_AND/PIP3_activates_AKT_signaling_Sept23_2016_sorted_checked_patched_1_NegativeORtoAND.txt --analyze-known-si-list

julia scripts/analyzeBioNetwork.jl ~/git/PGM/Pathways_where_negative_OR_is_AND/PIP3_activates_AKT_signaling_Sept23_2016_sorted_checked_patched_1_NegativeORtoAND.txt ~/git/PGM/InputDataForTesting/Mock_Short_Input_Data_for_PIP3_Activates_AKT_Signaling_Text.txt

inspecting results from observation file

julia scripts/analyzeBioNetwork.jl ~/git/PGM/Pathways_where_negative_OR_is_AND/PIP3_activates_AKT_signaling_Sept23_2016_sorted_checked_patched_1_NegativeORtoAND.txt ~/git/PGM/InputDataForTesting/Mock_Short_Input_Data_for_PIP3_Activates_AKT_Signaling_Text.txt <results-file> ~/git/PGM/Expected_results_for_mock_input_data/PIP3_activates_AKT_signaling_Expected_Results_for_Mock_input_Data.csv

Making Environment container

make build-env

Run Development

make run-bash

This command will run bash inside a pre-specified docker envionment. Feel free to copy the command and specify your desired environment

create Tsne Plot

1. start interactive server
2. Start julia repl

julia

3. Install tsne package

Pkg.clone("git://github.com/lejon/TSne.jl.git")

4. Exit repl

exit()

4. Run tsne command

Make sure the subgroup_label is the name of the column that you are using to categorize the rows

julia scripts/create_tsne_plot.jl haveheader --labelcolname=subgroup_label /data/gecco/mpbiopath_results.summary.observation.subgroup.tsv

This will generate a file in working directory called Plot2.png.

5. Move image to mounted volume