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Recent assemblies by the T2T and VGP consortia have achieved significant accuracy but required a tremendous amount of effort and resources. More typical assembly efforts, on the other hand, still suffer both from misassemblies (joining sequences that should not be adjacent) and from underassemblies (not joining sequences that should be adjacent). To better understand the common algorithm-driven causes of these limitations, we investigated the unitig algorithm, which is a core algorithm at the heart of most assemblers. We prove that, contrary to popular belief, even when there are no sequencing errors, unitigs are not always safe (i.e., they are not guaranteed to be substrings of the sequenced genome). We also prove that the unitigs of a bidirected de Bruijn graph are different from those of a doubled de Bruijn graph and, contrary to our expectations, result in underassembly. Using experimental simulations, we then confirm that these two artifacts exist not only in theory but also in the output of widely used assemblers. In particular, when coverage is low, then even error-free data result in unsafe unitigs; also, unitigs may unnecessarily split palindromes in half if special care is not taken. To the best of our knowledge, this paper is the first to theoretically predict the existence of these assembler artifacts and confirm and measure the extent of their occurrence in practice.more » « less
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Abstract Motivation The third-generation DNA sequencing technologies, such as Nanopore Sequencing, can operate at very high speeds and produce longer reads, which in turn results in a challenge for the computational analysis of such massive data. Nanopolish is a software package for signal-level analysis of Oxford Nanopore sequencing data. Call-methylation module of Nanopolish can detect methylation based on Hidden Markov Model (HMM). However, Nanopolish is limited by the long running time of some serial and computationally expensive processes. Among these, Adaptive Banded Event Alignment (ABEA) is the most time-consuming step, and the prior work, f5c, has already parallelized and optimized ABEA on GPU. As a result, the remaining methylation score calculation part, which uses HMM to identify if a given base is methylated or not, has become the new performance bottleneck.
Results This article focuses on the call-methylation module that resides in the Nanopolish package. We propose Galaxy-methyl, which parallelizes and optimizes the methylation score calculation step on GPU and then pipelines the four steps of the call-methylation module. Galaxy-methyl increases the execution concurrency across CPUs and GPUs as well as hardware resource utilization for both. The experimental results collected indicate that Galaxy-methyl can achieve 3×–5× speedup compared with Nanopolish, and reduce the total execution time by 35% compared with f5c, on average.
Availability and implementation The source code of Galaxy-methyl is available at https://github.com/fengyilin118/.
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Abstract Summary Bioinformatics applications increasingly rely on ad hoc disk storage of k-mer sets, e.g. for de Bruijn graphs or alignment indexes. Here, we introduce the K-mer File Format as a general lossless framework for storing and manipulating k-mer sets, realizing space savings of 3–5× compared to other formats, and bringing interoperability across tools.
Availability and implementation Format specification, C++/Rust API, tools: https://github.com/Kmer-File-Format/.
Supplementary information Supplementary data are available at Bioinformatics online.
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