Compute diffusion scores over networks from biological databases

## Introduction

DiffuPath is an analytic tool for biological networks that connects the generic label propagation algorithms from DiffuPy to biological networks encoded in several formats such as Simple Interaction Format (SIF) or Biological Expression Language (BEL). For example, in the application scenario presented in the paper, we use three pathway databases (i.e., KEGG, Reactome and WikiPathways) and their integrated network retrieved from PathMe [1] to analyze three multi-omics datasets. However, other biological networks can be imported from the Bio2BEL ecosystem [2].

### Installation

The latest stable code can be installed from PyPI with:

$python3 -m pip install diffupath The most recent code can be installed from the source on GitHub with: $ python3 -m pip install git+https://github.com/multipaths/diffupath.git

For developers, the repository can be cloned from GitHub and installed in editable mode with:

$git clone https://github.com/multipaths/diffupath.git$ cd diffupath
$python3 -m pip install -e . ### Requirements diffupath requires the following libraries: networkx (>=2.1) pybel (0.13.2) biokeen (0.0.14) click (7.0) tqdm (4.31.1) numpy (1.16.3) scipy (1.2.1) scikit-learn (0.21.3) pandas (0.24.2) openpyxl (3.0.2) plotly (4.5.3) matplotlib (3.1.2) matplotlib_venn (0.11.5) bio2bel (0.2.1) pathme diffupy ### Command Line Interface The following commands can be used directly from your terminal: 1. Download a database for network analysis. The following command generates a BEL file representing the network of the given database. $ python3 -m diffupath database get-database --database=<database-name>

To check the available databases, run the following command:

$python3 -m diffupath database ls 1. Run a diffusion analysis The following command will run a diffusion method on a given network with the given data $ python3 -m diffupath diffusion diffuse --network=<path-to-network-file> --data=<path-to-data-file> --method=<method>
1. Run a diffusion analysis

\$ python3 -m diffupath diffusion evaluate -i=<input_data> -n=<path_network>

### Input Data

You can submit your dataset in any of the following formats:

• CSV (.csv)

• TSV (.tsv)

Please ensure that the dataset minimally has a column ‘Node’ containing node IDs. You can also optionally add the following columns to your dataset:

• NodeType

• LogFC [*]

• p-value

#### Input dataset examples

DiffuPath accepts several input formats which can be codified in different ways. See the diffusion scores summary for more details.

1. You can provide a dataset with a column ‘Node’ containing node IDs.

Node

A

B

C

D

2. You can also provide a dataset with a column ‘Node’ containing node IDs as well as a column ‘NodeType’, indicating the entity type of the node to run diffusion by entity type.

Node

NodeType

A

Gene

B

Gene

C

Metabolite

D

Gene

3. You can also choose to provide a dataset with a column ‘Node’ containing node IDs as well as a column ‘logFC’ with their LogFC. You may also add a ‘NodeType’ column to run diffusion by entity type.

Node

LogFC

A

4

B

-1

C

1.5

D

3

4. Finally, you can provide a dataset with a column ‘Node’ containing node IDs, a column ‘logFC’ with their logFC and a column ‘p-value’ with adjusted p-values. You may also add a ‘NodeType’ column to run diffusion by entity type.

Node

LogFC

p-value

A

4

0.03

B

-1

0.05

C

1.5

0.001

D

3

0.07

You can also take a look at our sample datasets folder for some examples files.

### Networks

In this section, we describe the types of networks you can select to run diffusion methods over. These include the following and are described in detail in this section []:

• Select a network representing an individual biological database

• Select multiple databases to generate a harmonized network

• Select from one of four predefined collections of biological databases representing a harmonized network

• Submit your own network [] from one of the accepted formats

#### Network Dumps

Because of the high computational cost of generating the kernel, we provide links to pre-calculated kernels for a set of networks representing biological databases.

Database

Description

Reference

DDR

Disease-disease associations

[3]

ddr.json

DrugBank

Drug and drug target interactions

[4]

drugbank.json

Gene Ontology

Hierarchy of tens of thousands of biological processes

[5]

go.json

HSDN

Associations between diseases and symptoms

[6]

hsdn.json

KEGG

Multi-omics interactions in biological pathways

[7]

kegg.json

miRTarBase

Interactions between miRNA and their targets

[8]

mirtarbase.json

Reactome

Multi-omics interactions in biological pathways

[9]

reactome.json

SIDER

Associations between drugs and side effects

[10]

sider.json

WikiPathways

Multi-omics interactions in biological pathways

[11]

wikipathways.json

If you would like to use one of our predefined collections, you can similarly download pre-calculated kernels for sets of networks representing integrated biological databases.

Collection

Database

Description

#1

KEGG, Reactome and WikiPathways

-omics and biological processes/pathways

pathme.json

#2

KEGG, Reactome, WikiPathways and DrugBank

-omics and biological processes/pathways with a strong focus on drug/chemical interactions

pathme_drugbank.json

#3

KEGG, Reactome, WikiPathways and MirTarBase

-omics and biological processes/ pathways enriched with miRNAs

pathme_mirtarbase.json

#### Custom-network formats

You can also submit your own networks in any of the following formats:

• BEL (.bel)

• CSV (.csv)

• Edge list (.lst)

• GML (.gml or .xml)

• GraphML (.graphml or .xml)

• Pickle (.pickle)

• TSV (.tsv)

• TXT (.txt)

Minimally, please ensure each of the following columns are included in the network file you submit:

• Source

• Target

Optionally, you can choose to add a third column, “Relation” in your network (as in the example below). If the relation between the Source and Target nodes is omitted, and/or if the directionality is ambiguous, either node can be assigned as the Source or Target.

#### Custom-network example

Source

Target

Relation

A

B

Increase

B

C

Association

A

D

Association

You can also take a look at our sample networks folder for some examples.

### Disclaimer

DiffuPath is a scientific software that has been developed in an academic capacity, and thus comes with no warranty or guarantee of maintenance, support, or back-up of data.

## Project details

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