Large-scale population variant data is often used to filter and aid interpretation of variant calls in a single sample. These approaches do not incorporate population information directly into the process of variant calling, and are often limited to filtering which trades recall for precision. In this study, we develop population-aware DeepVariant models with a new channel encoding allele frequencies from the 1000 Genomes Project. This model reduces variant calling errors, improving both precision and recall in single samples, and reduces rare homozygous and pathogenic clinvar calls cohort-wide. We assess the use of population-specific or diverse reference panels, finding the greatest accuracy with diverse panels, suggesting that large, diverse panels are preferable to individual populations, even when the population matches sample ancestry. Finally, we show that this benefit generalizes to samples with different ancestry from the training data even when the ancestry is also excluded from the reference panel.

MOTIVATION: As more population genetics datasets and population-specific references become available, the task of translating ('lifting') read alignments from one reference coordinate system to another is becoming more common. Existing tools generally require a chain file, whereas VCF files are the more common way to represent variation. Existing tools also do not make effective use of threads, creating a post-alignment bottleneck. RESULTS: LevioSAM is a tool for lifting SAM/BAM alignments from one reference to another using a VCF file containing population variants. LevioSAM uses succinct data structures and scales efficiently to many threads. When run downstream of a read aligner, levioSAM is more than 7 times faster than an aligner when both are run with 16 threads. AVAILABILITY AND IMPLEMENTATION: Software Package: https://github.com/alshai/levioSAM, Experiments: https://github.com/langmead-lab/levioSAM-experiments. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

In this paper, we propose hardware-compatible Adaptively Banded Smith-Waterman algorithm (ABSW) to align long genomic sequences. By utilizing banded Smith-Waterman algorithm to align subsequences of fixed lengths, ABSW finds alignment of a pair of arbitrarily long sequences with constant memory. In addition, a heuristic algorithm, dynamic overlapping, is proposed to make overlaps of bands of subsequences to improve accuracy. To enable hardware acceleration of ABSW, we further propose the hardware architecture of banded Smith-Waterman with traceback. Experiments show that ABSW produces near optimal alignment scores for sequences with up to 40% error rates. Our hardware implementation of ABSW demonstrates more than 200× speedup over software implementation.

FM-index is an efficient data structure for string search and is widely used in next-generation sequencing (NGS) applications such as sequence alignment and de novo assembly. Recently, FM-indexing is even performed down to the read level, raising a demand of an efficient algorithm for FM-index construction. In this work, we propose a hardware-compatible Self-Aided Incremental Indexing (SAII) algorithm and its hard-ware architecture. This novel algorithm builds FM-index with no memory overhead, and the hardware system for realizing the algorithm can be very compact. Parallel architecture and a special prefetch controller is designed to enhance computational efficiency. An SAII-based FM-index constructor is implemented on an Altera Stratix V FPGA board. The presented constructor can support DNA sequences of sizes up to 131,072-bp, which is enough for small-scale references and reads obtained from current major platforms. Because the proposed constructor needs very few hardware resource, it can be easily integrated into different hardware accelerators designed for FM-index-based applications.

In this paper, we design a special-purpose processor for pairwise alignment and propose to integrate this design into a Multiple Sequence Alignment (MSA) flow. The processor is based on a modified algorithm of Banded Two-Hit Basic Local Alignment Search Tool for Nucleotides (MB2-BLASTn). In the new hybrid MSA flow, our MB2-BLASTn processor is used to find pairwise alignment first. Then the results are sent to CPUs for tree-building and progressive alignment. Since the pairwise alignment takes about 90% of total computing time in the original software flow, 100X speedup achieved by MB2-BLASTn can greatly improve the speed of MSA.