Browsing by Author "Alser, M."
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Item Open Access Accelerating genome analysis: a primer on an ongoing journey(IEEE, 2020) Alser, M.; Zülal, Bingöl; Cali, D. S.; Kim, J.; Ghose, S.; Alkan, Can; Mutlu, OnurGenome analysis fundamentally starts with a process known as read mapping, where sequenced fragments of an organism's genome are compared against a reference genome. Read mapping is currently a major bottleneck in the entire genome analysis pipeline, because state-of-the-art genome sequencing technologies are able to sequence a genome much faster than the computational techniques employed to analyze the genome. We describe the ongoing journey in significantly improving the performance of read mapping. We explain state-of-the-art algorithmic methods and hardware-based acceleration approaches. Algorithmic approaches exploit the structure of the genome as well as the structure of the underlying hardware. Hardware-based acceleration approaches exploit specialized microarchitectures or various execution paradigms (e.g., processing inside or near memory). We conclude with the challenges of adopting these hardware-accelerated read mappers.Item Open Access Apollo: A sequencing-technology-independent, scalable and accurate assembly polishing algorithm(Oxford University Press, 2020-03) Fırtına, C.; Kim, J. S.; Alser, M.; Şenol Cali, D.; Çiçek, A. Ercüment; Alkan, Can; Mutlu, OnurMotivation: Third-generation sequencing technologies can sequence long reads that contain as many as 2 million base pairs. These long reads are used to construct an assembly (i.e. the subject’s genome), which is further used in downstream genome analysis. Unfortunately, third-generation sequencing technologies have high sequencing error rates and a large proportion of base pairs in these long reads is 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, current assembly polishing algorithms can only polish an assembly using reads from either a certain sequencing technology or a small assembly. Such technologydependency and assembly-size dependency require researchers to (i) run multiple polishing algorithms and (ii) use small chunks of a large genome to use all available readsets and polish large genomes, respectively. Results: 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 thirdgeneration). 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 (i) models an assembly as a profile hidden Markov model (pHMM), (ii) uses read-to-assembly alignment to train the pHMM with the Forward– Backward algorithm and (iii) decodes the trained model with the Viterbi algorithm to produce a polished assembly. Our experiments with real readsets demonstrate that Apollo is the only algorithm that (i) uses reads from any sequencing technology within a single run and (ii) scales well to polish large assemblies without splitting the assembly into multiple parts.Item Open Access BLEND: A fast, memory-efficient and accurate mechanism to find fuzzy seed matches in genome analysis(Oxford University Press, 2023-01-10) Firtina, C.; Park, J.; Alser, M.; Kim, J. S.; Cali, D. S.; Shahroodi, T.; Ghiasi, N. M.; Singh, G.; Kanellopoulos, K.; Alkan, Can; Mutlu, O.Generating the hash values of short subsequences, called seeds, enables quickly identifying similarities between genomic sequences by matching seeds with a single lookup of their hash values. However, these hash values can be used only for finding exact-matching seeds as the conventional hashing methods assign distinct hash values for different seeds, including highly similar seeds. Finding only exact-matching seeds causes either (i) increasing the use of the costly sequence alignment or (ii) limited sensitivity. We introduce BLEND, the first efficient and accurate mechanism that can identify both exact-matching and highly similar seeds with a single lookup of their hash values, called fuzzy seed matches. BLEND (i) utilizes a technique called SimHash, that can generate the same hash value for similar sets, and (ii) provides the proper mechanisms for using seeds as sets with the SimHash technique to find fuzzy seed matches efficiently. We show the benefits of BLEND when used in read overlapping and read mapping. For read overlapping, BLEND is faster by 2.4×-83.9× (on average 19.3×), has a lower memory footprint by 0.9×-14.1× (on average 3.8×), and finds higher quality overlaps leading to accurate de novo assemblies than the state-of-the-art tool, minimap2. For read mapping, BLEND is faster by 0.8×-4.1× (on average 1.7×) than minimap2. Source code is available at https://github.com/CMU-SAFARI/BLEND. © 2023 The Author(s). Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.Item Open Access GateKeeper: a new hardware architecture for accelerating pre-alignment in DNA short read mapping(Oxford University Press, 2017-11-01) Alser, M.; Hassan, H.; Xin, H.; Ergin, O.; Mutlu, O.; Alkan C.High throughput DNA sequencing (HTS) technologies generate an excessive number of small DNA segments -called short reads- that cause significant computational burden. To analyze the entire genome, each of the billions of short reads must be mapped to a reference genome based on the similarity between a read and ‘candidate’ locations in that reference genome. The similarity measurement, called alignment, formulated as an approximate string matching problem, is the computational bottleneck because: (i) it is implemented using quadratic-time dynamic programming algorithms and (ii) the majority of candidate locations in the reference genome do not align with a given read due to high dissimilarity. Calculating the alignment of such incorrect candidate locations consumes an overwhelming majority of a modern read mapper’s execution time. Therefore, it is crucial to develop a fast and effective filter that can detect incorrect candidate locations and eliminate them before invoking computationally costly alignment algorithms.Item Open Access GenASM: a high-performance, low-power approximate string matching acceleration framework for genome sequence analysis(IEEE Computer Society, 2020) Şenol-Çalı, D.; Kalsi, G. S.; Bingöl, Zülal; Fırtına, C.; Subramanian, L.; Kim, J. S.; Ausavarungnirun, R.; Alser, M.; Gomez-Luna, J.; Boroumand, A.; Norion, A.; Scibisz, A.; Subramoneyon, S.; Alkan, Can; Ghose, S.; Mutlu, OnurGenome sequence analysis has enabled significant advancements in medical and scientific areas such as personalized medicine, outbreak tracing, and the understanding of evolution. To perform genome sequencing, devices extract small random fragments of an organism's DNA sequence (known as reads). The first step of genome sequence analysis is a computational process known as read mapping. In read mapping, each fragment is matched to its potential location in the reference genome with the goal of identifying the original location of each read in the genome. Unfortunately, rapid genome sequencing is currently bottlenecked by the computational power and memory bandwidth limitations of existing systems, as many of the steps in genome sequence analysis must process a large amount of data. A major contributor to this bottleneck is approximate string matching (ASM), which is used at multiple points during the mapping process. ASM enables read mapping to account for sequencing errors and genetic variations in the reads. We propose GenASM, the first ASM acceleration framework for genome sequence analysis. GenASM performs bitvectorbased ASM, which can efficiently accelerate multiple steps of genome sequence analysis. We modify the underlying ASM algorithm (Bitap) to significantly increase its parallelism and reduce its memory footprint. Using this modified algorithm, we design the first hardware accelerator for Bitap. Our hardware accelerator consists of specialized systolic-array-based compute units and on-chip SRAMs that are designed to match the rate of computation with memory capacity and bandwidth, resulting in an efficient design whose performance scales linearly as we increase the number of compute units working in parallel. We demonstrate that GenASM provides significant performance and power benefits for three different use cases in genome sequence analysis. First, GenASM accelerates read alignment for both long reads and short reads. For long reads, GenASM outperforms state-of-the-art software and hardware accelerators by 116× and 3.9×, respectively, while reducing power consumption by 37× and 2.7×. For short reads, GenASM outperforms state-of-the-art software and hardware accelerators by 111× and 1.9×. Second, GenASM accelerates pre-alignment filtering for short reads, with 3.7× the performance of a state-of-the-art pre-alignment filter, while reducing power consumption by 1.7× and significantly improving the filtering accuracy. Third, GenASM accelerates edit distance calculation, with 22-12501× and 9.3-400× speedups over the state-of-the-art software library and FPGA-based accelerator, respectively, while reducing power consumption by 548-582× and 67×. We conclude that GenASM is a flexible, high-performance, and low-power framework, and we briefly discuss four other use cases that can benefit from GenASM.Item Open Access GRIM-Filter: fast seed location filtering in DNA read mapping using processing-in-memory technologies(BioMed Central, 2018) Kim, J. S.; Cali, D. S.; Xin, H.; Lee, D.; Ghose, S.; Alser, M.; Hassan, H.; Ergin, O.; Alkan C.; Mutlu, O.Background: Seed location filtering is critical in DNA read mapping, a process where billions of DNA fragments (reads) sampled from a donor are mapped onto a reference genome to identify genomic variants of the donor. State-of-the-art read mappers 1) quickly generate possible mapping locations for seeds (i.e., smaller segments) within each read, 2) extract reference sequences at each of the mapping locations, and 3) check similarity between each read and its associated reference sequences with a computationally-expensive algorithm (i.e., sequence alignment) to determine the origin of the read. A seed location filter comes into play before alignment, discarding seed locations that alignment would deem a poor match. The ideal seed location filter would discard all poor match locations prior to alignment such that there is no wasted computation on unnecessary alignments. Results: We propose a novel seed location filtering algorithm, GRIM-Filter, optimized to exploit 3D-stacked memory systems that integrate computation within a logic layer stacked under memory layers, to perform processing-in-memory (PIM). GRIM-Filter quickly filters seed locations by 1) introducing a new representation of coarse-grained segments of the reference genome, and 2) using massively-parallel in-memory operations to identify read presence within each coarse-grained segment. Our evaluations show that for a sequence alignment error tolerance of 0.05, GRIM-Filter 1) reduces the false negative rate of filtering by 5.59x-6.41x, and 2) provides an end-to-end read mapper speedup of 1.81x-3.65x, compared to a state-of-the-art read mapper employing the best previous seed location filtering algorithm. Conclusion: GRIM-Filter exploits 3D-stacked memory, which enables the efficient use of processing-in-memory, to overcome the memory bandwidth bottleneck in seed location filtering. We show that GRIM-Filter significantly improves the performance of a state-of-the-art read mapper. GRIM-Filter is a universal seed location filter that can be applied to any read mapper. We hope that our results provide inspiration for new works to design other bioinformatics algorithms that take advantage of emerging technologies and new processing paradigms, such as processing-in-memory using 3D-stacked memory devices.Item Open Access MAGNET: understanding and improving the accuracy of genome pre-alignment filtering(I P S I, 2017) Alser, M.; Mutlu, O.; Alkan C.In the era of high throughput DNA sequencing (HTS) technologies, calculating the edit distance (i.e.,the minimum number of substitutions, insertions, and deletionsbetween a pair of sequences) forbillions of genomicsequences is the computational bottleneck intoday’s read mappers. The shifted Hamming distance (SHD) algorithm proposes afast filtering strategy that can rapidly filter out invalid mappings that have more edits than allowed. However, SHD shows high inaccuracy in its filtering by admitting invalid mappings to be marked as correct ones. This wastesthe execution time and imposesa large computational burden. In this work, we comprehensively investigate foursources that lead to the filtering inaccuracy. We propose MAGNET, anewfiltering strategy that maintains high accuracy across different edit distance thresholds and data sets. It significantly improvestheaccuracy of pre-alignment filtering by one to twoordersof magnitude.The MATLAB implementationsof MAGNETand SHDareopen source and available at:https://github.com/BilkentCompGen/MAGNET.Item Open Access SeGraM: A universal hardware accelerator for genomic sequence-to-graph and sequence-to-sequence mapping(Association for Computing Machinery, 2020-06-11) Cali, D.Ş; Kanellopoulos, K.; Lindegger, J.; Bingöl, Zülal; Kalsi, G.S.; Zuo, Z.; Fırtına, Can; Cavlak, M.B.; Kim, J.; Ghiasi, N.M.; Singh, G.; Gómez-Luna, J.; Almadhoun Alserr, N.; Alser, M.; Subramoney, S.; Alkan, Can; Ghose, S.; Mutlu, O.A critical step of genome sequence analysis is the mapping of sequenced DNA fragments (i.e., reads) collected from an individual to a known linear reference genome sequence (i.e., sequence-to-sequence mapping). Recent works replace the linear reference sequence with a graph-based representation of the reference genome, which captures the genetic variations and diversity across many individuals in a population. Mapping reads to the graph-based reference genome (i.e., sequence-to-graph mapping) results in notable quality improvements in genome analysis. Unfortunately, while sequence-to-sequence mapping is well studied with many available tools and accelerators, sequence-to-graph mapping is a more difficult computational problem, with a much smaller number of practical software tools currently available. We analyze two state-of-the-art sequence-to-graph mapping tools and reveal four key issues. We find that there is a pressing need to have a specialized, high-performance, scalable, and low-cost algorithm/hardware co-design that alleviates bottlenecks in both the seeding and alignment steps of sequence-to-graph mapping. Since sequence-to-sequence mapping can be treated as a special case of sequence-to-graph mapping, we aim to design an accelerator that is efficient for both linear and graph-based read mapping. To this end, we propose SeGraM, a universal algorithm/hardware co-designed genomic mapping accelerator that can effectively and efficiently support both sequence-to-graph mapping and sequence-to-sequence mapping, for both short and long reads. To our knowledge, SeGraM is the first algorithm/hardware co-design for accelerating sequence-to-graph mapping. SeGraM consists of two main components: (1) MinSeed, the first minimizer-based seeding accelerator, which finds the candidate locations in a given genome graph; and (2) BitAlign, the first bitvector-based sequence-to-graph alignment accelerator, which performs alignment between a given read and the subgraph identified by MinSeed. We couple SeGraM with high-bandwidth memory to exploit low latency and highly-parallel memory access, which alleviates the memory bottleneck. We demonstrate that SeGraM provides significant improvements for multiple steps of the sequence-to-graph (i.e., S2G) and sequence-to-sequence (i.e., S2S) mapping pipelines. First, SeGraM outperforms state-of-the-art S2G mapping tools by 5.9×/3.9× and 106×/- 742× for long and short reads, respectively, while reducing power consumption by 4.1×/4.4× and 3.0×/3.2×. Second, BitAlign outperforms a state-of-the-art S2G alignment tool by 41×-539× and three S2S alignment accelerators by 1.2×-4.8×. We conclude that SeGraM is a high-performance and low-cost universal genomics mapping accelerator that efficiently supports both sequence-to-graph and sequence-to-sequence mapping pipelines.