Browsing by Author "Mutlu, O."
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Item Open Access Accelerating read mapping with FastHASH(BioMed Central Ltd., 2013) Xin, H.; Lee, D.; Hormozdiari, F.; Yedkar, S.; Mutlu, O.; Alkan C.With the introduction of next-generation sequencing (NGS) technologies, we are facing an exponential increase in the amount of genomic sequence data. The success of all medical and genetic applications of next-generation sequencing critically depends on the existence of computational techniques that can process and analyze the enormous amount of sequence data quickly and accurately. Unfortunately, the current read mapping algorithms have difficulties in coping with the massive amounts of data generated by NGS. We propose a new algorithm, FastHASH, which drastically improves the performance of the seed-and-extend type hash table based read mapping algorithms, while maintaining the high sensitivity and comprehensiveness of such methods. FastHASH is a generic algorithm compatible with all seed-and-extend class read mapping algorithms. It introduces two main techniques, namely Adjacency Filtering, and Cheap K-mer Selection. We implemented FastHASH and merged it into the codebase of the popular read mapping program, mrFAST. Depending on the edit distance cutoffs, we observed up to 19-fold speedup while still maintaining 100% sensitivity and high comprehensiveness. © 2013 Xin et al.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 Fast and accurate mapping of complete genomics reads(Academic Press, 2015) Lee, D.; Hormozdiari, F.; Xin, H.; Hach, F.; Mutlu, O.; Alkan C.Many recent advances in genomics and the expectations of personalized medicine are made possible thanks to power of high throughput sequencing (HTS) in sequencing large collections of human genomes. There are tens of different sequencing technologies currently available, and each HTS platform have different strengths and biases. This diversity both makes it possible to use different technologies to correct for shortcomings; but also requires to develop different algorithms for each platform due to the differences in data types and error models. The first problem to tackle in analyzing HTS data for resequencing applications is the read mapping stage, where many tools have been developed for the most popular HTS methods, but publicly available and open source aligners are still lacking for the Complete Genomics (CG) platform. Unfortunately, Burrows-Wheeler based methods are not practical for CG data due to the gapped nature of the reads generated by this method. Here we provide a sensitive read mapper (sirFAST) for the CG technology based on the seed-and-extend paradigm that can quickly map CG reads to a reference genome. We evaluate the performance and accuracy of sirFAST using both simulated and publicly available real data sets, showing high precision and recall rates.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 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 Nanopore sequencing technology and tools for genome assembly: computational analysis of the current state, bottlenecks and future directions(Oxford University Press, 2018-04) Cali, D. S.; Kim, J. S.; Ghose, S.; Alkan, Can; Mutlu, O.Nanopore sequencing technology has the potential to render other sequencing technologies obsolete with its ability to generate long reads and provide portability. However, high error rates of the technology pose a challenge while generating accurate genome assemblies. The tools used for nanopore sequence analysis are of critical importance, as they should overcome the high error rates of the technology. Our goal in this work is to comprehensively analyze current publicly available tools for nanopore sequence analysis to understand their advantages, disadvantages and performance bottlenecks. It is important to understand where the current tools do not perform well to develop better tools. To this end, we (1) analyze the multiple steps and the associated tools in the genome assembly pipeline using nanopore sequence data, and (2) provide guidelines for determining the appropriate tools for each step. Based on our analyses, we make four key observations: (1) the choice of the tool for basecalling plays a critical role in overcoming the high error rates of nanopore sequencing technology. (2) Read-to-read overlap finding tools, GraphMap and Minimap, perform similarly in terms of accuracy. However, Minimap has a lower memory usage, and it is faster than GraphMap. (3) There is a trade-off between accuracy and performance when deciding on the appropriate tool for the assembly step. The fast but less accurate assembler Miniasm can be used for quick initial assembly, and further polishing can be applied on top of it to increase the accuracy, which leads to faster overall assembly. (4) The state-of-the-art polishing tool, Racon, generates high-quality consensus sequences while providing a significant speedup over another polishing tool, Nanopolish. We analyze various combinations of different tools and expose the trade-offs between accuracy, performance, memory usage and scalability. We conclude that our observations can guide researchers and practitioners in making conscious and effective choices for each step of the genome assembly pipeline using nanopore sequence data. Also, with the help of bottlenecks we have found, developers can improve the current tools or build new ones that are both accurate and fast, to overcome the high error rates of the nanopore sequencing technology.Item Open Access Optimal seed solver: optimizing seed selection in read mapping(Oxford University Press, 2016) Xin, H.; Nahar, S.; Zhu, R.; Emmons, J.; Pekhimenko, G.; Kingsford, C.; Alkan C.; Mutlu, O.Motivation: Optimizing seed selection is an important problem in read mapping. The number of non-overlapping seeds a mapper selects determines the sensitivity of the mapper while the total frequency of all selected seeds determines the speed of the mapper. Modern seed-and-extend mappers usually select seeds with either an equal and fixed-length scheme or with an inflexible placement scheme, both of which limit the ability of the mapper in selecting less frequent seeds to speed up the mapping process. Therefore, it is crucial to develop a new algorithm that can adjust both the individual seed length and the seed placement, as well as derive less frequent seeds. Results: We present the Optimal Seed Solver (OSS), a dynamic programming algorithm that discovers the least frequently-occurring set of x seeds in an L-base-pair read in O(x×L) operations on average and in O(x×L2) operations in the worst case, while generating a maximum of O(L2) seed frequency database lookups. We compare OSS against four state-of-the-art seed selection schemes and observe that OSS provides a 3-fold reduction in average seed frequency over the best previous seed selection optimizations. Availability and implementation: We provide an implementation of the Optimal Seed Solver in C++ at: https://github.com/CMU-SAFARI/Optimal-Seed-Solver. Supplementary information: Supplementary data are available at Bioinformatics online.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.Item Open Access Shifted Hamming distance: a fast and accurate SIMD-friendly filter to accelerate alignment verification in read mapping(Oxford University Press, 2015) Xin, H.; Greth, J.; Emmons, J.; Pekhimenko, G.; Kingsford, C.; Alkan C.; Mutlu, O.Motivation: Calculating the edit-distance (i.e. minimum number of insertions, deletions and substitutions) between short DNA sequences is the primary task performed by seed-and-extend based mappers, which compare billions of sequences. In practice, only sequence pairs with a small edit-distance provide useful scientific data. However, the majority of sequence pairs analyzed by seed-and-extend based mappers differ by significantly more errors than what is typically allowed. Such error-abundant sequence pairs needlessly waste resources and severely hinder the performance of read mappers. Therefore, it is crucial to develop a fast and accurate filter that can rapidly and efficiently detect error-abundant string pairs and remove them from consideration before more computationally expensive methods are used. Results: We present a simple and efficient algorithm, Shifted Hamming Distance (SHD), which accelerates the alignment verification procedure in read mapping, by quickly filtering out error-abundant sequence pairs using bit-parallel and SIMD-parallel operations. SHD only filters string pairs that contain more errors than a user-defined threshold, making it fully comprehensive. It also maintains high accuracy with moderate error threshold (up to 5% of the string length) while achieving a 3-fold speedup over the best previous algorithm (Gene Myers's bit-vector algorithm). SHD is compatible with all mappers that perform sequence alignment for verification.