PuffAligner: a fast, efficient and accurate aligner based on the Pufferfish index
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Updated: Nov 2, 2025

Author Spotlight: 3D Movement Assessment of Maxillary Posterior Teeth in Clear Aligner Treatment
Published on: February 23, 2024
Fatemeh Almodaresi1, Mohsen Zakeri1, Rob Patro1
1Computer Science Department, University of Maryland, College Park, MD 20742, USA.
Motivation:
Sequence alignment is one of the first steps in many modern genomic analyses, such as variant detection, transcript abundance estimation and metagenomic profiling. Unfortunately, it is often a computationally expensive procedure. As the quantity of data and wealth of different assays and applications continue to grow, the need for accurate and fast alignment tools that scale to large collections of reference sequences persists.
Results:
In this article, we introduce PuffAligner, a fast, accurate and versatile aligner built on top of the Pufferfish index. PuffAligner is able to produce highly sensitive alignments, similar to those of Bowtie2, but much more quickly. While exhibiting similar speed to the ultrafast STAR aligner, PuffAligner requires considerably less memory to construct its index and align reads. PuffAligner strikes a desirable balance with respect to the time, space and accuracy tradeoffs made by different alignment tools and provides a promising foundation on which to test new alignment ideas over large collections of sequences.
Availability And Implementation:
All the data used for preparing the results of this paper can be found with 10.5281/zenodo.4902332. PuffAligner is a free and open-source software. It is implemented in C++14 and can be obtained from https://github.com/COMBINE-lab/pufferfish/tree/cigar-strings.
Supplementary Information:
Supplementary data are available at Bioinformatics online.
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