Dear MEGAN Development Team,
I would like to request a clarification regarding the terminology used to describe frameshift alignment in the DIAMOND–MEGAN workflow.
During the peer-review process of a recent manuscript, a reviewer questioned the term “frameshift alignment,” arguing that frameshifts themselves are not aligned. The reviewer suggested that “frameshift-tolerant alignment” would more accurately describe the computational process.
I recognize that the terminology “frame-shift alignment” and “frame-shift aware DNA-to-protein alignment” has been explicitly used in peer-reviewed publications by the DIAMOND developers, including:
- Arumugam et al. (2019). Annotated bacterial chromosomes from frame-shift-corrected long-read metagenomic data. Microbiome, 7:61. Client Challenge
- Buchfink et al. (2021). Sensitive protein alignments at tree-of-life scale using DIAMOND. Nature Methods, 18:366–368. Sensitive protein alignments at tree-of-life scale using DIAMOND | Nature Methods
However, the reviewer’s observation raises an important question about the precision and consistency of terminology, particularly for researchers unfamiliar with the underlying alignment algorithms.
Would the development team consider standardizing the terminology in future documentation, manuals, and software descriptions to something more explicit, such as:
“Frameshift-aware translated DNA-to-protein sequence alignment”
or
“Frameshift-tolerant DNA-to-protein sequence alignment”?
These descriptions would emphasize that DIAMOND performs sequence alignment while allowing reading-frame transitions, rather than suggesting that frameshift events themselves are being aligned.
I understand that “frameshift alignment” is already an established term in computational biology, and I am not suggesting that the terminology is scientifically incorrect. Rather, introducing more descriptive language might improve methodological clarity, particularly in interdisciplinary metagenomics research and scientific publications.
I would also appreciate the developers’ perspective on whether “frameshift-aware alignment” is the preferred terminology for describing DIAMOND’s --frameshift (-F) functionality in the Methods sections of peer-reviewed manuscripts.
Thank you for developing and maintaining these valuable bioinformatics tools and for considering this suggestion.
Best regards
Nitin