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-18x 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.

Automated summary

This study introduces an automated approach for configuring k-mer-based error correction tools by evaluating perplexity metric of corrected reads. The results show that the optimal k-mer value can vary for different datasets, with lower perplexity indicating better k-mer size and strong negative correlation with alignment rate and assembly quality. The study also demonstrates significant runtime improvement using attention-based models in the entire pipeline.