Cuterle

Cuterle is a bioinformatic tool which creates an output file (extracted_domain.fasta) containing every domain annotated by InterProScan (~.tsv file) via Pfam or SMART analysis from the list of protein (~.fasta file) submitted.

This program use two main analysis of InterPro (here the others):

• Pfam (XX.X) : A large collection of protein families, each represented by multiple sequence alignments and hidden Markov models (HMMs)
• SMART (X.X) : SMART allows the identification and analysis of domain architectures based on Hidden Markov Models or HMMs

The choice between these two are based on which one has more results in ~.tsv file.

Index

• Suggested use
  
• Limitations
  
• Getting started
  
• Usage - Manual mode
  
• Examples manual mode syntax
  
• Usage - Assisted mode
  
• Output example - Fasta list
  
• Output example - Sequence's draw
  
• How to get a ~.tsv file
  
• Next updates
  

Suggested use

This program has been written thinking as improvement of quality of life for extracting the domains.

Exempli gratia
I want to investigate the relationship between the domains of multiple species:

1. Download the transcriptome of my species target
2. For each transcriptome obtain a new proteins' fasta list via hmmsearch from HMMER
3. Run an InterPro analysis for each sequences in every fasta list
4. Run Cuterle to extract every domain from each sequences choosing an InterPro accession ID for automatic domains' extraction (e.g. IPR002035)
5. Run some MSA and phylogenetic analysis to get some hint about the domain of interest

Thanks to the arguments option, the point 2, 3 and 4 are scriptable, saving A LOT of time.

Limitations

The biggest limitation is that Cuterle choose between Pfam and SMART at the beginning of the program, and not evaluating it for every protein (see Next updates).

This program does nothing more than extracting the domains identified by InterPro, choosing which analysis get more results.

This program **has not** been thought to replace software which perform protein analysis, like SMART.

Getting started

Prerequisites

• Python3
• pip

Installation of the Python required packages

Install the required Python packages; while you are in the project's root directory run the following command:

# Install requirements
pip install -r requirements.txt

Usage - Manual mode

From the release 1.2.0 it's available the manual mode, making the program script-friendly.

Asking help to the program:

python3 main.py -h

usage: main.py  [options]

-----------------------------------------------------------------
IF NO OPTION IS SELECTED, THE PROGRAM WILL RUN IN [ASSISTED MODE]
-----------------------------------------------------------------
DESCRIPTION

    Cuterle is a bioinformatic tool.
    It returns an output file containing every domain annotated by InterProScan.
    Pfam or SMART analysis are choosen by which method has more matches.

LIST OF OUTPUT FILE

    extracted_domains.fasta - contains every domains extracted
    [optional] domains_list.csv - contains the table's raw data (domain_name,count)
    [optional] domains_view[seq_name].jpg - schematic domains draw FOR EACH sequence

NAME FORMAT
    The name for every sequence added to extracted_domain.fasta is [>1,2,3,4,5,6]

        1 - Protein accession (e.g. P51587)
        2 - Length of the domain (e.g. [DOMAIN LENGHT: (150)])
        3 - Start location of the domain (e.g. [START: 50])
        4 - End location of the domain (e.g. [END: 200])
        5 - InterPro annotations - description (e.g. [BRCA2 repeat])
        6 - InterPro accession (e.g. [IPR002035])

    It is possible to CHANGE the order for every tag;
        e.g. [-nf 1] or [-nf 1,2,3,4] or [-nf 5,4,3,2,6,2,2,1]
    DO NOT USE SPACE between the number!
------------------------------------------

optional arguments:
  -h, --help         show this help message and exit
  -m                 Enable the manual mode. -tsv and -fasta argument are requested
  -tsv file.tsv      Input file containing the tsv file output from InterPro
  -fasta file.fasta  Input file containing the fasta sequences
  -a Pfam or SMART   Prior choice between 'Pfam' and 'SMART'. Read the documentation.
  -nf NF             Name format. Read the documentation. Format: [1,2,3,4,5,6]
  -accession ACCESSION  InterPro annotations - accession (e.g. IPR002035)
  -savetable         Export all kind of domains extracted in ~.csv file, sort by matches
  -draw_image        FOR EACH sequences create a ~.jpg file reporting sequence+domains

Examples manual mode syntax

python3 main.py -m -tsv vwf_Homo_sapiens.tsv -fasta vwf_Homo_sapiens.fasta -nf 1,2,3 -savetable -drawimage

python3 main.py -m -tsv vwf_Homo_sapiens.tsv -fasta vwf_Homo_sapiens.fasta -a SMART -nf 6,2,1,2,3 -accession IPR002035

Usage - Assisted mode

In terminal run:

python3 main.py

If no optional argument is given, the program will run the assisted mode.
Assisted mode is a lot verbose.

Once you run main.py in terminal, the program request the two input files (~.tsv and ~.fasta).
For every input file there is a check which guarantee its existence and the right format.
Please be sure to use the right format

If you are not sure about how getting the tsv file follow How to get a ~.tsv file.

Summary table ("Accession ID", "Domain name" and "Domains' number found" as header) is graphically printed. It's possible to save it.

Output example - Fasta list

All the extracted domains have the follow default syntax:

• >[{1}] - [LENGTH: {2}] - [START: {3}] - [END: {4}] - [{5}] - [{6}] - First line
• extracted domain sequence - Second line

Where every {number} refer to the follow information:

• {1} - Protein accession (e.g. P51587)
• {2} - Length of the domain (e.g. [DOMAIN LENGHT: (150)])
• {3} - Start location of the domain (e.g. [START: 50])
• {4} - End location of the domain (e.g. [END: 200])
• {5} - InterPro annotations - description (e.g. [BRCA2 repeat])
• {6} - Signature accession (e.g. [IPR002035])

It's possible to change the syntax only by running the manual mode (or manual editing the code).

Output example - Sequence's draw

Every domain has a default color which is the same for all the proteins. There are 9 color; if there are more domains, they wll be colored in gray.

Draw layout:

• Sequence name
• Scale applied (if the scale is 1, it's hidden)
• Draw of the protein with its domains

How to get a ~.tsv file

There are two main way to get an tsv file from InterPro:

1. Follow the InterProScan guide to install and run it on some local machine

2. Use the official InterProScan website to submit the fasta fasta file and obtain the tsv file (like in the screenshot below):

3. 

Next updates

TOP PRIORITY

• Adding a GUI
• Re-organization of all the code in function, allowing the creation of GUI.
• Change the way Cuterle choose the analysis (from once-at-start to protein-to-protein choice)

MEDIUM PRIORITY

• None

LOW PRIORITY

• AppImage release?