Fast approximation of frequent \(k\)-mers and applications to metagenomics. (English) Zbl 1412.92209

Cowen, Lenore J. (ed.), Research in computational molecular biology. 23rd annual international conference, RECOMB 2019, Washington, DC, USA, May 5–8, 2019. Proceedings. Cham: Springer. Lect. Notes Comput. Sci. 11467, 208-226 (2019).
Summary: Estimating the abundances of all \(k\)-mers in a set of biological sequences is a fundamental and challenging problem with many applications in biological analysis. While several methods have been designed for the exact or approximate solution of this problem, they all require to process the entire dataset, that can be extremely expensive for high-throughput sequencing datasets. While in some applications it is crucial to estimate all \(k\)-mers and their abundances, in other situations reporting only frequent \(k\)-mers, that appear with relatively high frequency in a dataset, may suffice. This is the case, for example, in the computation of \(k\)-mers’ abundance-based distances among datasets of reads, commonly used in metagenomic analyses.
In this work, we develop, analyze, and test, a sampling-based approach, called SAKEIMA, to approximate the frequent \(k\)-mers and their frequencies in a high-throughput sequencing dataset while providing rigorous guarantees on the quality of the approximation. SAKEIMA employs an advanced sampling scheme and we show how the characterization of the VC dimension, a core concept from statistical learning theory, of a properly defined set of functions leads to practical bounds on the sample size required for a rigorous approximation. Our experimental evaluation shows that SAKEIMA allows to rigorously approximate frequent \(k\)-mers by processing only a fraction of a dataset and that the frequencies estimated by SAKEIMA lead to accurate estimates of \(k\)-mer based distances between high-throughput sequencing datasets. Overall, SAKEIMA is an efficient and rigorous tool to estimate \(k\)-mers abundances providing significant speed-ups in the analysis of large sequencing datasets.
For the entire collection see [Zbl 1408.92004].


92D10 Genetics and epigenetics
92-04 Software, source code, etc. for problems pertaining to biology
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