[Paper Review] MAP Format for Representing Chemical Modifications, Annotations, and Mutations in Protein Sequences: An Extension of the FASTA Format

Aditi Shendre, Naman Kumar Mehta+4 more|ArXiv.org|May 6, 2025

Genetics, Bioinformatics, and Biomedical Research5 citations

TL;DR

MAP is a new protein sequence format extending FASTA to encode chemical modifications, annotations, and mutations via header meta tags and inline residue tags.

ABSTRACT

Several formats, including FASTA, PIR, GenBank, EMBL, and GCG, have been developed for representing protein sequences composed of natural amino acids. Among these, FASTA remains the most widely used due to its simplicity and human readability. However, FASTA lacks the capability to represent chemically modified or non-natural residues, as well as structural annotations and mutations in protein variants. To address some of these limitations, the PEFF format was recently introduced as an extension of FASTA. Additionally, formats such as HELM and BILN have been proposed to represent amino acids and their modifications at the atomic level. Despite their advancements, these formats have not achieved widespread adoption within the bioinformatics community due to their complexity. To complement existing formats and overcome current challenges, we propose a new format called MAP (Modification and Annotation in Proteins), which enables comprehensive annotation of protein sequences. MAP introduces meta tags in the header for protein-level annotations and inline tags within the sequence for residue-level modifications. In this format, standard one-letter amino acid codes are augmented with curly-brace tags to denote various modifications, including phosphorylation, acetylation, non-natural residues, cyclization, and other residue-specific features. The header metadata also captures information such as organism, function, and sequence variants. We describe the structure, objectives, and capabilities of the MAP format and demonstrate its application in bioinformatics, particularly in the domain of protein therapeutics. To facilitate community adoption, we are developing a comprehensive suite of MAP-format resources, including a detailed manual, annotated datasets, and conversion tools, available at http://webs.iiitd.edu.in/raghava/maprepo/.

Motivation & Objective

• Enable comprehensive annotation of protein sequences beyond natural amino acids.
• Provide a practical, readable format that supports modifications, non-natural residues, and mutations.
• Complement existing formats (e.g., PEFF) with a simpler, adoption-friendly approach.

Proposed method

• Introduce header-level meta tags for protein annotations (organism, function, variants).
• Introduce inline curly-brace tags appended to standard one-letter amino acid codes to denote residue-level modifications.
• Describe supported modification types (e.g., phosphorylation, acetylation, non-natural residues, cyclization).
• Explain the structure and capabilities of MAP and its intended bioinformatics applications.
• Outline plans for community resources: manual, annotated datasets, and conversion tools.

Experimental results

Research questions

• RQ1 How does MAP encode residue-level modifications within protein sequences?
• RQ2 What header metadata are required or supported for protein annotations and variants?
• RQ3 How does MAP compare to existing formats like PEFF, HELM, and BILN in terms of usability and adoption potential?
• RQ4 Can MAP be effectively applied to areas such as protein therapeutics and variant annotation?

Key findings

• MAP introduces header meta tags and inline residue-level curly-brace tags to represent modifications and annotations in protein sequences.
• MAP supports a range of residue-specific features including phosphorylation, acetylation, non-natural residues, and cyclization.
• The format is described in terms of structure, objectives, and capabilities, with demonstrated relevance to protein therapeutics.
• The authors are developing a broader MAP ecosystem, including a detailed manual, annotated datasets, and conversion tools.
• MAP is positioned as a complementary extension to FASTA to address limitations of existing formats.