InterProScan 6: a modern large-scale protein function annotation pipeline
Matthias Blum1, Emma Hobbs1, Laise Florentino1
1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, CB10 1SD, United Kingdom.
Bioinformatics Advances
|June 1, 2026
Summary
InterProScan 6, a Nextflow pipeline, enhances protein function annotation by improving scalability and reproducibility. This new version offers faster analysis and integrates modern predictors for efficient genome-scale protein classification.
Area of Science:
- Bioinformatics
- Computational Biology
- Genomics
Background:
- InterProScan 5 is a widely used tool for protein function classification, integral to major annotation pipelines.
- InterProScan 5 faced challenges in scalability, installation, data management, and workflow integration.
Purpose of the Study:
- To present InterProScan 6, a reimplementation addressing InterProScan 5's limitations.
- To enhance scalability, portability, and reproducibility of protein annotation across diverse computational environments.
Main Methods:
- Reimplemented InterProScan as a Nextflow pipeline.
- Decoupled application code from signature data.
- Integrated native container support, on-demand data management, and deep-learning predictors.
- Developed a redesigned Matches API for JSON annotation retrieval.
Main Results:
- InterProScan 6 demonstrated approximately two-fold speedups on large eukaryotic proteomes compared to InterProScan 5.
- Runtimes were reduced to minutes when using the Matches API for pre-computed annotations.
- InterProScan 6 reproduced InterProScan 5 results with near-identical precision and sensitivity.
Conclusions:
- InterProScan 6 provides a more efficient, flexible, and reproducible solution for genome-scale protein function annotation.
- The Nextflow implementation enhances usability across local, HPC, and cloud platforms.
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These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
02:26Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
02:04Protein-protein Interfaces
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...
01:33Proteomics
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Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term proteomics...
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03:36Genome Annotation and Assembly
The genome refers to all of the genetic material in an organism. It can range from a few million base pairs in microbial cells to several billion base pairs in many eukaryotic organisms. Genome assembly refers to the process of taking the DNA sequencing data and putting it all back together in a correct order to create a close representation of the original genome. This is followed by the identification of functional elements on the newly assembled genome, a process called genome annotation.