An efficient error correction algorithm using FM-index.

High-throughput sequencing offers higher throughput and lower cost for sequencing a genome. However, sequencing errors, including mismatches and indels, may be produced during sequencing. Because, errors may reduce the accuracy of subsequent de novo assembly, error correction is necessary prior to assembly. However, existing correction methods still face trade-offs among correction power, accuracy, and speed. We develop a novel overlap-based error correction algorithm using FM-index (called FMOE). FMOE first identifies overlapping reads by aligning a query read simultaneously against multiple reads compressed by FM-index. Subsequently, sequencing errors are corrected by k-mer voting from overlapping reads only. The experimental results indicate that FMOE has highest correction power with comparable accuracy and speed. Our algorithm performs better in long-read than short-read datasets when compared with others. The assembly results indicated different algorithms has its own strength and weakness, whereas FMOE is good for long or good-quality reads. FMOE is freely available at https://github.com/ythuang0522/FMOC .

Huang YT ，Huang YW 《BMC BIOINFORMATICS》

Improving the sensitivity of long read overlap detection using grouped short k-mer matches.

Du N ，Chen J ，Sun Y 《BMC GENOMICS》

Lerna: transformer architectures for configuring error correction tools for short- and long-read genome sequencing.

Sequencing technologies are prone to errors, making error correction (EC) necessary for downstream applications. EC tools need to be manually configured for optimal performance. We find that the optimal parameters (e.g., k-mer size) are both tool- and dataset-dependent. Moreover, evaluating the performance (i.e., Alignment-rate or Gain) of a given tool usually relies on a reference genome, but quality reference genomes are not always available. We introduce Lerna for the automated configuration of k-mer-based EC tools. Lerna first creates a language model (LM) of the uncorrected genomic reads, and then, based on this LM, calculates a metric called the perplexity metric to evaluate the corrected reads for different parameter choices. Next, it finds the one that produces the highest alignment rate without using a reference genome. The fundamental intuition of our approach is that the perplexity metric is inversely correlated with the quality of the assembly after error correction. Therefore, Lerna leverages the perplexity metric for automated tuning of k-mer sizes without needing a reference genome. First, we show that the best k-mer value can vary for different datasets, even for the same EC tool. This motivates our design that automates k-mer size selection without using a reference genome. Second, we show the gains of our LM using its component attention-based transformers. We show the model's estimation of the perplexity metric before and after error correction. The lower the perplexity after correction, the better the k-mer size. We also show that the alignment rate and assembly quality computed for the corrected reads are strongly negatively correlated with the perplexity, enabling the automated selection of k-mer values for better error correction, and hence, improved assembly quality. We validate our approach on both short and long reads. Additionally, we show that our attention-based models have significant runtime improvement for the entire pipeline-18[Formula: see text] faster than previous works, due to parallelizing the attention mechanism and the use of JIT compilation for GPU inferencing. Lerna improves de novo genome assembly by optimizing EC tools. Our code is made available in a public repository at: https://github.com/icanforce/lerna-genomics .

Sharma A ，Jain P ，Mahgoub A ，Zhou Z ，Mahadik K ，Chaterji S ... -  《BMC BIOINFORMATICS》

Iterative error correction of long sequencing reads maximizes accuracy and improves contig assembly.

Next-generation sequencers such as Illumina can now produce reads up to 300 bp with high throughput, which is attractive for genome assembly. A first step in genome assembly is to computationally correct sequencing errors. However, correcting all errors in these longer reads is challenging. Here, we show that reads with remaining errors after correction often overlap repeats, where short erroneous k-mers occur in other copies of the repeat. We developed an iterative error correction pipeline that runs the previously published String Graph Assembler (SGA) in multiple rounds of k-mer-based correction with an increasing k-mer size, followed by a final round of overlap-based correction. By combining the advantages of small and large k-mers, this approach corrects more errors in repeats and minimizes the total amount of erroneous reads. We show that higher read accuracy increases contig lengths two to three times. We provide SGA-Iteratively Correcting Errors (https://github.com/hillerlab/IterativeErrorCorrection/) that implements iterative error correction by using modules from SGA.

Sameith K ，Roscito JG ，Hiller M 《-》

A hybrid and scalable error correction algorithm for indel and substitution errors of long reads.

Long-read sequencing has shown the promises to overcome the short length limitations of second-generation sequencing by providing more complete assembly. However, the computation of the long sequencing reads is challenged by their higher error rates (e.g., 13% vs. 1%) and higher cost ($0.3 vs. $0.03 per Mbp) compared to the short reads. In this paper, we present a new hybrid error correction tool, called ParLECH (Parallel Long-read Error Correction using Hybrid methodology). The error correction algorithm of ParLECH is distributed in nature and efficiently utilizes the k-mer coverage information of high throughput Illumina short-read sequences to rectify the PacBio long-read sequences.ParLECH first constructs a de Bruijn graph from the short reads, and then replaces the indel error regions of the long reads with their corresponding widest path (or maximum min-coverage path) in the short read-based de Bruijn graph. ParLECH then utilizes the k-mer coverage information of the short reads to divide each long read into a sequence of low and high coverage regions, followed by a majority voting to rectify each substituted error base. ParLECH outperforms latest state-of-the-art hybrid error correction methods on real PacBio datasets. Our experimental evaluation results demonstrate that ParLECH can correct large-scale real-world datasets in an accurate and scalable manner. ParLECH can correct the indel errors of human genome PacBio long reads (312 GB) with Illumina short reads (452 GB) in less than 29 h using 128 compute nodes. ParLECH can align more than 92% bases of an E. coli PacBio dataset with the reference genome, proving its accuracy. ParLECH can scale to over terabytes of sequencing data using hundreds of computing nodes. The proposed hybrid error correction methodology is novel and rectifies both indel and substitution errors present in the original long reads or newly introduced by the short reads.

Das AK ，Goswami S ，Lee K ，Park SJ ... -  《BMC GENOMICS》