Can Alkan

Meryem Banu Cavlak, Gagandeep Singh, Mohammed Alser et al.

Basecalling is an essential step in nanopore sequencing analysis where the raw signals of nanopore sequencers are converted into nucleotide sequences, i.e., reads. State-of-the-art basecallers employ complex deep learning models to achieve high basecalling accuracy. This makes basecalling computationally inefficient and memory-hungry, bottlenecking the entire genome analysis pipeline. However, for many applications, the majority of reads do no match the reference genome of interest (i.e., target reference) and thus are discarded in later steps in the genomics pipeline, wasting the basecalling computation. To overcome this issue, we propose TargetCall, the first pre-basecalling filter to eliminate the wasted computation in basecalling. TargetCall's key idea is to discard reads that will not match the target reference (i.e., off-target reads) prior to basecalling. TargetCall consists of two main components: (1) LightCall, a lightweight neural network basecaller that produces noisy reads; and (2) Similarity Check, which labels each of these noisy reads as on-target or off-target by matching them to the target reference. Our thorough experimental evaluations show that TargetCall 1) improves the end-to-end basecalling runtime performance of the state-of-the-art basecaller by 3.31x while maintaining high (98.88%) recall in keeping on-target reads, 2) maintains high accuracy in downstream analysis, and 3) achieves better runtime performance, throughput, recall, precision, and generality compared to prior works. TargetCall is available at https://github.com/CMU-SAFARI/TargetCall.

Jeremie S. Kim, Can Firtina, Meryem Banu Cavlak et al.

AirLift is the first read remapping tool that enables users to quickly and comprehensively map a read set, that had been previously mapped to one reference genome, to another similar reference. Users can then quickly run a downstream analysis of read sets for each latest reference release. Compared to the state-of-the-art method for remapping reads (i.e., full mapping), AirLift reduces the overall execution time to remap read sets between two reference genome versions by up to 27.4x. We validate our remapping results with GATK and find that AirLift provides high accuracy in identifying ground truth SNP/INDEL variants AirLift source code and readme describing how to reproduce our results are available at https://github.com/CMU-SAFARI/AirLift.

Adrian Tkachenko, Sepehr Salem, Ayotomiwa Ezekiel Adeniyi et al.

Motivation: High-throughput sequencing (HTS) enables population-scale genomics but generates massive datasets, creating bottlenecks in storage, transfer, and analysis. FASTQ, the standard format for over two decades, stores one byte per base and one byte per quality score, leading to inefficient I/O, high storage costs, and redundancy. Existing compression tools can mitigate some issues, but often introduce costly decompression or complex dependency issues. Results: We introduce FASTR, a lossless, computation-native successor to FASTQ that encodes each nucleotide together with its base quality score into a single 8-bit value. FASTR reduces file size by at least 2x while remaining fully reversible and directly usable for downstream analyses. Applying general-purpose compression tools on FASTR consistently yields higher compression ratios, 2.47, 3.64, and 4.8x faster compression, and 2.34, 1.96, 1.75x faster decompression than on FASTQ across Illumina, HiFi, and ONT reads. FASTR is machine-learning-ready, allowing reads to be consumed directly as numerical vectors or image-like representations. We provide a highly parallel software ecosystem for FASTQ-FASTR conversion and show that FASTR integrates with existing tools, such as minimap2, with minimal interface changes and no performance overhead. By eliminating decompression costs and reducing data movement, FASTR lays the foundation for scalable genomics analyses and real-time sequencing workflows. Availability and Implementation: https://github.com/ALSER-Lab/FASTR

Zuher Jahshan, Can Alkan, Leonid Yavits

Real-time viral genome detection, taxonomic classification and phylogenetic analysis are critical for efficient tracking and control of viral pandemics such as Covid-19. However, the unprecedented and still growing amounts of viral genome data create a computational bottleneck, which effectively prevents the real-time pandemic tracking. For genomic tracing to work effectively, each new viral genome sequence must be placed in its pangenomic context. Re-inferring the full phylogeny of SARS-CoV-2, with datasets containing millions of samples, is prohibitively slow even using powerful computational resources. We are attempting to alleviate the computational bottleneck by modifying and applying Vision Transformer, a recently developed neural network model for image recognition, to taxonomic classification and placement of viral genomes, such as SARS-CoV-2. Our solution, CoViT, places SARS-CoV-2 genome accessions onto SARS-CoV-2 phylogenetic tree with the accuracy of 94.2%. Since CoViT is a classification neural network, it provides more than one likely placement. Specifically, one of the two most likely placements suggested by CoViT is correct with the probability of 97.9%. The probability of the correct placement to be found among the five most likely placements generated by CoViT is 99.8%. The placement time is 0.055s per individual genome running on NVIDIAs GeForce RTX 2080 Ti GPU. We make CoViT available to research community through GitHub: https://github.com/zuherJahshan/covit.

William Andrew Simon, Leonid Yavits, Konstantina Koliogeorgi et al.

Low-cost, high-throughput DNA and RNA sequencing (HTS) data is the backbone of the life sciences. Genome sequencing is now becoming a part of Predictive, Preventive, Personalized, and Participatory (termed 'P4') medicine. All genomic data are currently processed in energy-hungry computer clusters and centers, necessitating data transfer, consuming substantial energy, and wasting valuable time. Therefore, there is a need for fast, energy-efficient, and cost-efficient technologies that enable genomics research without requiring data centers and cloud platforms. We recently launched the BioPIM Project to leverage emerging processing-in-memory (PIM) technologies to enable energy- and cost-efficient analysis of bioinformatics workloads. The BioPIM Project focuses on co-designing algorithms and data structures commonly used in genomics with several PIM architectures to achieve the highest cost, energy, and time savings.

Can Firtina, Jeremie S. Kim, Mohammed Alser et al.

Long reads produced by third-generation sequencing technologies are used to construct an assembly (i.e., the subject's genome), which is further used in downstream genome analysis. Unfortunately, long reads have high sequencing error rates and a large proportion of bps in these long reads are incorrectly identified. These errors propagate to the assembly and affect the accuracy of genome analysis. Assembly polishing algorithms minimize such error propagation by polishing or fixing errors in the assembly by using information from alignments between reads and the assembly (i.e., read-to-assembly alignment information). However, assembly polishing algorithms can only polish an assembly using reads either from a certain sequencing technology or from a small assembly. Such technology-dependency and assembly-size dependency require researchers to 1) run multiple polishing algorithms and 2) use small chunks of a large genome to use all available read sets and polish large genomes. We introduce Apollo, a universal assembly polishing algorithm that scales well to polish an assembly of any size (i.e., both large and small genomes) using reads from all sequencing technologies (i.e., second- and third-generation). Our goal is to provide a single algorithm that uses read sets from all available sequencing technologies to improve the accuracy of assembly polishing and that can polish large genomes. Apollo 1) models an assembly as a profile hidden Markov model (pHMM), 2) uses read-to-assembly alignment to train the pHMM with the Forward-Backward algorithm, and 3) decodes the trained model with the Viterbi algorithm to produce a polished assembly. Our experiments with real read sets demonstrate that Apollo is the only algorithm that 1) uses reads from any sequencing technology within a single run and 2) scales well to polish large assemblies without splitting the assembly into multiple parts.

Atalay M. Ileri, Halil I. Ozercan, Alper Gundogdu et al.

Rate of growth of the amount of data generated using the high throughput sequencing (HTS) platforms now exceeds the growth stipulated by Moore's Law. The HTS data is expected to surpass those of other "big data" domains such as astronomy, before the year 2025. In addition to sequencing genomes for research purposes, genome and exome sequencing in clinical settings will be a routine part of health care. The analysis of such large amounts of data, however, is not without computational challenges. This burden is even more increased due to the periodic updates to reference genomes, which typically require re-analysis of existing data. Here we propose Coin-Application Mediator Interface (Coinami) to distribute the workload for mapping reads to reference genomes using a volunteer grid computer approach similar to Berkeley Open Infrastructure for Network Computing (BOINC). However, since HTS read mapping requires substantial computational resources and fast analysis turnout is desired, Coinami uses the HTS read mapping as proof-of-work to generate valid blocks to main its own cryptocurrency system, which may help motivate volunteers to dedicate more resources. The Coinami protocol includes mechanisms to ensure that jobs performed by volunteers are correct, and provides genomic data privacy. The prototype implementation of Coinami is available at http://coinami.github.io/.