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RAM-MSA: an anytime memory-bounded method for exact multiple sequence alignment using path finding.

Jue Wang1, Fumihiko Ino1

  • 1Graduate School of Information Science and Technology, The University of Osaka, Suita, Osaka 565-0871, Japan.

Bioinformatics Advances
|July 1, 2026
PubMed
Summary

A new exact multiple sequence alignment (MSA) method, RAM-MSA, provides accurate alignments with reduced memory usage. It offers anytime performance, delivering initial results quickly and improving them to an exact solution, even with affine gap penalties.

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Area of Science:

  • Bioinformatics and Computational Biology
  • Genomics and Proteomics
  • Algorithm Development

Background:

  • Multiple sequence alignment (MSA) is vital for analyzing DNA and protein sequences to understand biological relationships.
  • Existing exact MSA methods face memory limitations with increasing sequence numbers, while heuristic methods sacrifice accuracy.
  • There is a need for an exact MSA approach balancing accuracy and computational resources.

Purpose of the Study:

  • To introduce Recursive Anytime Memory-bounded MSA (RAM-MSA), an exact MSA method designed to overcome memory constraints.
  • To enable users to obtain optimal sequence alignments within practical computational timeframes.
  • To address the limitations of existing MSA techniques in terms of memory efficiency and accuracy.

Main Methods:

  • Developed Recursive Anytime Memory-bounded MSA (RAM-MSA), an exact algorithm for multiple sequence alignment.
  • Implemented memory-bounding techniques to manage exponential memory demands.
  • Extended functionality to handle affine gap penalties, unlike previous methods.

Main Results:

  • RAM-MSA significantly reduced memory usage by 62.51% compared to state-of-the-art exact methods.
  • The method achieved an initial alignment score of 0.96 rapidly, comparable to heuristic approaches.
  • RAM-MSA continuously refines alignments towards the exact solution and supports affine gap penalties.

Conclusions:

  • RAM-MSA offers an effective solution for exact multiple sequence alignment, addressing memory and time constraints.
  • The 'anytime' nature of RAM-MSA allows for practical application in large-scale bioinformatics analyses.
  • This work quantifies the difference between algorithmic and structural alignments.