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

BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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 .

Author Correction: Athena: Automated Tuning of k-mer based Genomic Error Correction Algorithms using Language Models.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Athena: Automated Tuning of k-mer based Genomic Error Correction Algorithms using Language Models.

The performance of most error-correction (EC) algorithms that operate on genomics reads is dependent on the proper choice of its configuration parameters, such as the value of k in k-mer based techniques. In this work, we target the problem of finding the best values of these configuration parameters to optimize error correction and consequently improve genome assembly. We perform this in an adaptive manner, adapted to different datasets and to EC tools, due to the observation that different configuration parameters are optimal for different datasets, i.e., from different platforms and species, and vary with the EC algorithm being applied. We use language modeling techniques from the Natural Language Processing (NLP) domain in our algorithmic suite, Athena, to automatically tune the performance-sensitive configuration parameters. Through the use of N-Gram and Recurrent Neural Network (RNN) language modeling, we validate the intuition that the EC performance can be computed quantitatively and efficiently using the "perplexity" metric, repurposed from NLP. After training the language model, we show that the perplexity metric calculated from a sample of the test (or production) data has a strong negative correlation with the quality of error correction of erroneous NGS reads. Therefore, we use the perplexity metric to guide a hill climbing-based search, converging toward the best configuration parameter value. Our approach is suitable for both de novo and comparative sequencing (resequencing), eliminating the need for a reference genome to serve as the ground truth. We find that Athena can automatically find the optimal value of k with a very high accuracy for 7 real datasets and using 3 different k-mer based EC algorithms, Lighter, Blue, and Racer. The inverse relation between the perplexity metric and alignment rate exists under all our tested conditions-for real and synthetic datasets, for all kinds of sequencing errors (insertion, deletion, and substitution), and for high and low error rates. The absolute value of that correlation is at least 73%. In our experiments, the best value of k found by Athena achieves an alignment rate within 0.53% of the oracle best value of k found through brute force searching (i.e., scanning through the entire range of k values). Athena's selected value of k lies within the top-3 best k values using N-Gram models and the top-5 best k values using RNN models With best parameter selection by Athena, the assembly quality (NG50) is improved by a Geometric Mean of 4.72X across the 7 real datasets.