Accurate consistency-based MSA reducing the memory footprint
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Updated: Oct 31, 2025

Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
Jordi Lladós1, Fernando Cores1, Fernando Guirado1
1INSPIRES Research Center, Universitat de Lleida. Jaume II. 69, 25001 Lleida, Spain.
Background And Objective:
The emergence of Next-Generation sequencing has created a push for faster and more accurate multiple sequence alignment tools. The growing number of sequences and their longer sizes, which require the use of increased system resources and produce less accurate results, are heavily challenging to these applications. Consistency-based methods have the most intensive CPU and memory usage requirements. We hypothesize that library reductions can enhance the scalability and performance of consistency-based multiple sequence alignment tools; however, we have previously shown a noticeable impact on the accuracy when extreme reductions were performed.
Methods:
In this study, we propose Matrix-Based T-Coffee, a consistency-based method that uses library reductions in conjunction with a complementary objective function. The proposed method, implemented in T-Coffee, can mitigate the accuracy loss caused by low memory resources.
Results:
The use of a complementary objective function with a library reduction of ≥30% improved the accuracy of T-Coffee. Interestingly, ≥50% library reduction achieved lower execution times and better overall scalability.
Conclusions:
Matrix-Based T-Coffee benefits from accurate alignments while achieving better scalability. This leads to a reduction in memory footprint and execution time. In addition, these enhancements could be applied to other aligners based on consistency.
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