AUTHOR=Zhai Yixiao , Zhang Zitong , Li Zhen TITLE=Advances in post-processing methods for multiple sequence alignment JOURNAL=Frontiers in Genetics VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2025.1722317 DOI=10.3389/fgene.2025.1722317 ISSN=1664-8021 ABSTRACT=The reliability of multiple sequence alignment (MSA) results directly determines the credibility of the conclusions drawn from biological research. However, MSA is inherently an NP-hard problem, making it theoretically impossible to guarantee a globally optimal solution. Consequently, in addition to developing more efficient alignment algorithms, improving the quality of initial alignments through post-processing optimization has become an important strategy for enhancing the overall alignment accuracy. Although post-processing methods have shown potential in improving alignment accuracy, currently, there is a lack of systematic reviews and summaries. In this review, we provide a systematic overview of the development and key research ideas of MSA post-processing methods over the past 3 decades and outline potential directions for future research.