MutClust 0.1.1

MutClust: Mutual rank-based coexpression, clustering and GO term enrichment analysis.

MutClust: Mutual Rank-Based Clustering and GO Enrichment Analysis

MutClust is a Python package designed for RNA-seq gene coexpression analyses. It performs mutual rank (MR)-based clustering of coexpressed genes and identifies enriched Gene Ontology (GO) terms for the resulting clusters. The package is optimized for speed, able to run a whole-genome coexpression analysis in minutes.

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Features

• Mutual Rank Analysis: Calculates MR from Pearson correlation coefficients to identify coexpressed genes.
• Leiden Clustering: Groups genes into clusters based on mutual rank and exponential decay weights.
• Gene Annotations: Merge cluster members with gene annotations, if provided.
• GO Enrichment Analysis: Identifies enriched GO terms for each cluster using GOATOOLS.
• Highly Configurable: Supports adjustable thresholds, resolution parameters, and multi-threading for performance optimization.

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Installation

TODO: You can install MutClust directly from PyPI:

pip install mutclust

Alternatively, you can clone the repository and install it locally:

git clone https://github.com/eporetsky/mutclust.git
cd mutclust
pip install .

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Usage

MutClust provides a command-line interface (CLI) for running the full pipeline. After installation, you can use the mutclust command.

Command-Line Arguments

Argument	Short	Description	Default
--expression	-ex	Path to the RNA-seq dataset (TSV format).	-ex or -mr required
--mutual_rank	-mr	Path to Mutual Rank file (TSV format).	-ex or -mr required
--annotations	-a	Path to the gene annotation file.	Optional
--go_obo	-go	Path to the Gene Ontology (GO) OBO file.	Optional
--go_gaf	-gf	Path to the GO annotation file (GAF format).	Optional
--output	-o	Output prefix for the results.	Required
--mr_threshold	-m	Mutual rank threshold for filtering.	100
--e_value	-e	Exponential decay constant.	10
--resolution	-r	Resolution parameter for Leiden clustering.	0.1
--threads	-t	Number of threads for correlation calculation.	4
--save_intermediate	-t	Number of threads for correlation calculation.	Optional

Example Command

mutclust --expression data/AtCol-0.cpm.tsv \
         --annotations annotations/AtCol-0.annot.tsv \
         --go_obo go-basic.obo \
         --go_gaf tair.gaf \
         --output results/mutclust_output \
         --mr_threshold 100 \
         --e_value 10 \
         --resolution 0.1 \
         --threads 8

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Input File Formats

RNA-seq Dataset

• Format: Tab-separated values (TSV).
• Columns: Gene IDs as row indices and samples as columns.
• Example:

geneID    Sample1    Sample2    Sample3
GeneA     1.23       2.34       3.45
GeneB     4.56       5.67       6.78

Gene Annotation File

• Format: Tab-separated values (TSV).
• Columns: geneID and additional annotation fields.
• Example:

geneID    description
GeneA     Photosynthesis-related protein
GeneB     Transcription factor

GO OBO File

• Description: The Gene Ontology (GO) OBO file contains the ontology structure.
• Source: Download from Gene Ontology.

GO GAF File

• Description: The Gene Annotation File (GAF) maps genes to GO terms.
• Source: Download from Gene Ontology.

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Output Files

1. Filtered MR and e-values (<output_prefix>.mrs.tsv):

   • Lists of coexpressed genes with MR and e-values.
   • Columns: cluster_id, geneID.

   Example:

   Gene1    Gene2    MR    ED
   GeneA    GeneB    10.2  0.39
   GeneB    GeneC    6     0.6
   

2. Clustered Genes (<output_prefix>.clusters.tsv):

   • Lists genes in each cluster.
   • Annotation columns if provided.
   • Columns: cluster_id, geneID.

   Example:

   cluster_id    geneID    Annotations
   1             GeneA     ...
   1             GeneB     ...
   

3. GO Enrichment Results (<output_prefix>_go_enrichment_results.tsv):

   • Contains enriched GO terms for each cluster.
   • Columns: cluster, type, size, term, p-val, FC, desc.

   Example:

   cluster    type    size    term       p-val       FC    desc
   1          BP      25      GO:0008150 0.00123     3.5   Biological Process
   

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Dependencies

The following Python libraries are required and will be installed automatically:

• numpy
• pandas
• pynetcor
• python-igraph
• goatools

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License

This project is licensed under the MIT License. See the LICENSE file for details.

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Contributing

Contributions, suggestions and issues are welcome!