arXiv subjects

Can Alkan

Publications and source records attributed to Can Alkan.

At least 19 recordsLinked to original sources

arXiv2026

FASTR: Reimagining FASTQ via Compact Image-inspired Representation

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

q-bio.GN↗

arXiv2025

LCPan: efficient variation graph construction using Locally Consistent Parsing

Efficient and consistent string processing is critical in the exponentially growing genomic data era. Locally Consistent Parsing (LCP) addresses this need by partitioning an input genome string into short, exactly matching substrings (e.g., "cores"), ensuring consistency across partitions. Labeling the cores of an input string consistently not only provides a compact representation of the input but also enables the reapplication of LCP to refine the cores over multiple iterations, providing a progressively longer and more informative set of substrings for downstream analyses. We present the first iterative implementation of LCP with Lcptools and demonstrate its effectiveness in identifying cores with minimal collisions. Experimental results show that the number of cores at the i^th iteration is O(n/c^i) for c ~ 2.34, while the average length and the average distance between consecutive cores are O(c^i). Compared to the popular sketching techniques, LCP produces significantly fewer cores, enabling a more compact representation and faster analyses. To demonstrate the advantages of LCP in genomic string processing in terms of computation and memory efficiency, we also introduce LCPan, an efficient variation graph constructor. We show that LCPan generates variation graphs >10x faster than vg, while using >13x less memory.

q-bio.GN↗

arXiv2025

Processing-in-memory for genomics workloads

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.

q-bio.GN↗

arXiv2023

Pairwise sequence alignment with block and character edit operations

Pairwise sequence comparison is one of the most fundamental problems in string processing. The most common metric to quantify the similarity between sequences S and T is edit distance, d(S,T), which corresponds to the number of characters that need to be substituted, deleted from, or inserted into S to generate T. However, fewer edit operations may be sufficient for some string pairs to transform one string to the other if larger rearrangements are permitted. Block edit distance refers to such changes in substring level (i.e., blocks) that "penalizes" entire block removals, insertions, copies, and reversals with the same cost as single-character edits (Lopresti & Tomkins, 1997). Most studies to calculate block edit distance to date aimed only to characterize the distance itself for applications in sequence nearest neighbor search without reporting the full alignment details. Although a few tools try to solve block edit distance for genomic sequences, such as GR-Aligner, they have limited functionality and are no longer maintained. Here, we present SABER, an algorithm to solve block edit distance that supports block deletions, block moves, and block reversals in addition to the classical single-character edit operations. Our algorithm runs in O(m^2.n.l_range) time for |S|=m, |T|=n and the permitted block size range of l_range; and can report all breakpoints for the block operations. We also provide an implementation of SABER currently optimized for genomic sequences (i.e., generated by the DNA alphabet), although the algorithm can theoretically be used for any alphabet. SABER is available at http://github.com/BilkentCompGen/saber

cs.DS↗

arXiv2023

GateSeeder: Near-memory CPU-FPGA Acceleration of Short and Long Read Mapping

Motivation: Read mapping is a computationally expensive process and a major bottleneck in genomics analyses. The performance of read mapping is mainly limited by the performance of three key computational steps: Index Querying, Seed Chaining, and Sequence Alignment. The first step is dominated by how fast and frequent it accesses the main memory (i.e., memory-bound), while the latter two steps are dominated by how fast the CPU can compute their computationally-costly dynamic programming algorithms (i.e., compute-bound). Accelerating these three steps by exploiting new algorithms and new hardware devices is essential to accelerate most genome analysis pipelines that widely use read mapping. Given the large body of work on accelerating Sequence Alignment, this work focuses on significantly improving the remaining steps. Results: We introduce GateSeeder, the first CPU-FPGA-based near-memory acceleration of both short and long read mapping. GateSeeder exploits near-memory computation capability provided by modern FPGAs that couple a reconfigurable compute fabric with high-bandwidth memory (HBM) to overcome the memory-bound and compute-bound bottlenecks. GateSeeder also introduces a new lightweight algorithm for finding the potential matching segment pairs. Using real ONT, HiFi, and Illumina sequences, we experimentally demonstrate that GateSeeder outperforms Minimap2, without performing sequence alignment, by up to 40.3x, 4.8x, and 2.3x, respectively. When performing read mapping with sequence alignment, GateSeeder outperforms Minimap2 by 1.15-4.33x (using KSW2) and by 1.97-13.63x (using WFA-GPU). Availability: https://github.com/CMU-SAFARI/GateSeeder

cs.AR↗

arXiv2022

TargetCall: Eliminating the Wasted Computation in Basecalling via Pre-Basecalling Filtering

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.

q-bio.GN↗

arXiv2022

CoViT: Real-time phylogenetics for the SARS-CoV-2 pandemic using Vision Transformers

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.

cs.LG↗

arXiv2022

SeGraM: A Universal Hardware Accelerator for Genomic Sequence-to-Graph and Sequence-to-Sequence Mapping

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. 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; and (2) BitAlign, the first bitvector-based sequence-to-graph alignment accelerator. We demonstrate that SeGraM provides significant improvements for multiple steps of the sequence-to-graph and sequence-to-sequence mapping pipelines.

cs.AR↗

arXiv2022

FastRemap: A Tool for Quickly Remapping Reads between Genome Assemblies

A genome read data set can be quickly and efficiently remapped from one reference to another similar reference (e.g., between two reference versions or two similar species) using a variety of tools, e.g., the commonly-used CrossMap tool. With the explosion of available genomic data sets and references, high-performance remapping tools will be even more important for keeping up with the computational demands of genome assembly and analysis. We provide FastRemap, a fast and efficient tool for remapping reads between genome assemblies. FastRemap provides up to a 7.82$\times$ speedup (6.47$\times$, on average) and uses as low as 61.7% (80.7%, on average) of the peak memory consumption compared to the state-of-the-art remapping tool, CrossMap. FastRemap is written in C++. The source code and user manual are freely available at: github.com/CMU-SAFARI/FastRemap. Docker image available at: https://hub.docker.com/r/alkanlab/fast. Also available in Bioconda at: https://anaconda.org/bioconda/fastremap-bio.

q-bio.GN↗

arXiv2021

BLEND: A Fast, Memory-Efficient, and Accurate Mechanism to Find Fuzzy Seed Matches in Genome Analysis

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 1) increasing the use of the costly sequence alignment or 2) 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 1) utilizes a technique called SimHash, that can generate the same hash value for similar sets, and 2) 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 2.4x - 83.9x (on average 19.3x), has a lower memory footprint by 0.9x - 14.1x (on average 3.8x), 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 0.8x - 4.1x (on average 1.7x) than minimap2. Source code is available at https://github.com/CMU-SAFARI/BLEND.

q-bio.GN↗

arXiv2021

GateKeeper-GPU: Fast and Accurate Pre-Alignment Filtering in Short Read Mapping

At the last step of short read mapping, the candidate locations of the reads on the reference genome are verified to compute their differences from the corresponding reference segments using sequence alignment algorithms. Calculating the similarities and differences between two sequences is still computationally expensive since approximate string matching techniques traditionally inherit dynamic programming algorithms with quadratic time and space complexity. We introduce GateKeeper-GPU, a fast and accurate pre-alignment filter that efficiently reduces the need for expensive sequence alignment. GateKeeper-GPU provides two main contributions: first, improving the filtering accuracy of GateKeeper (a lightweight pre-alignment filter), and second, exploiting the massive parallelism provided by the large number of GPU threads of modern GPUs to examine numerous sequence pairs rapidly and concurrently. By reducing the work, GateKeeper-GPU provides an acceleration of 2.9x to sequence alignment and up to 1.4x speedup to the end-to-end execution time of a comprehensive read mapper (mrFAST). GateKeeper-GPU is available at https://github.com/BilkentCompGen/GateKeeper-GPU.

q-bio.GN↗

arXiv2020

GateKeeper: A New Hardware Architecture for Accelerating Pre-Alignment in DNA Short Read Mapping

Motivation: 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: (1) it is implemented using quadratic-time dynamic programming algorithms, and (2) 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 operations. Results: We propose GateKeeper, a new hardware accelerator that functions as a pre-alignment step that quickly filters out most incorrect candidate locations. GateKeeper is the first design to accelerate pre-alignment using Field-Programmable Gate Arrays (FPGAs), which can perform pre-alignment much faster than software. GateKeeper can be integrated with any mapper that performs sequence alignment for verification. When implemented on a single FPGA chip, GateKeeper maintains high accuracy (on average >96%) while providing up to 90-fold and 130-fold speedup over the state-of-the-art software pre-alignment techniques, Adjacency Filter and Shifted Hamming Distance (SHD), respectively. The addition of GateKeeper as a pre-alignment step can reduce the verification time of the mrFAST mapper by a factor of 10. Availability: https://github.com/BilkentCompGen/GateKeeper

q-bio.GN↗

arXiv2020

Accelerating Genome Analysis: A Primer on an Ongoing Journey

Genome 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.

cs.AR↗

arXiv2020

GenASM: A High-Performance, Low-Power Approximate String Matching Acceleration Framework for Genome Sequence Analysis

Genome sequence analysis has enabled significant advancements in medical and scientific areas such as personalized medicine, outbreak tracing, and the understanding of evolution. Unfortunately, it 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). We propose GenASM, the first ASM acceleration framework for genome sequence analysis. We modify the underlying ASM algorithm (Bitap) to significantly increase its parallelism and reduce its memory footprint, and we design the first hardware accelerator for Bitap. Our hardware accelerator consists of specialized compute units and on-chip SRAMs that are designed to match the rate of computation with memory capacity and bandwidth. We demonstrate that GenASM is a flexible, high-performance, and low-power framework, which provides significant performance and power benefits for three different use cases in genome sequence analysis: 1) 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 116x and 3.9x, respectively, while consuming 37x and 2.7x less power. For short reads, GenASM outperforms state-of-the-art software and hardware accelerators by 111x and 1.9x. 2) GenASM accelerates pre-alignment filtering for short reads, with 3.7x the performance of a state-of-the-art pre-alignment filter, while consuming 1.7x less power and significantly improving the filtering accuracy. 3) GenASM accelerates edit distance calculation, with 22-12501x and 9.3-400x speedups over the state-of-the-art software library and FPGA-based accelerator, respectively, while consuming 548-582x and 67x less power.

cs.AR↗

arXiv2020

Apollo: A Sequencing-Technology-Independent, Scalable, and Accurate Assembly Polishing Algorithm

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.

q-bio.GN↗

arXiv2020

Technology dictates algorithms: Recent developments in read alignment

Massively parallel sequencing techniques have revolutionized biological and medical sciences by providing unprecedented insight into the genomes of humans, animals, and microbes. Modern sequencing platforms generate enormous amounts of genomic data in the form of nucleotide sequences or reads. Aligning reads onto reference genomes enables the identification of individual-specific genetic variants and is an essential step of the majority of genomic analysis pipelines. Aligned reads are essential for answering important biological questions, such as detecting mutations driving various human diseases and complex traits as well as identifying species present in metagenomic samples. The read alignment problem is extremely challenging due to the large size of analyzed datasets and numerous technological limitations of sequencing platforms, and researchers have developed novel bioinformatics algorithms to tackle these difficulties. Importantly, computational algorithms have evolved and diversified in accordance with technological advances, leading to todays diverse array of bioinformatics tools. Our review provides a survey of algorithmic foundations and methodologies across 107 alignment methods published between 1988 and 2020, for both short and long reads. We provide rigorous experimental evaluation of 11 read aligners to demonstrate the effect of these underlying algorithms on speed and efficiency of read aligners. We separately discuss how longer read lengths produce unique advantages and limitations to read alignment techniques. We also discuss how general alignment algorithms have been tailored to the specific needs of various domains in biology, including whole transcriptome, adaptive immune repertoire, and human microbiome studies.

q-bio.GN↗

arXiv2019

AirLift: A Fast and Comprehensive Technique for Remapping Alignments between Reference Genomes

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.

q-bio.GN↗

arXiv2019

SneakySnake: A Fast and Accurate Universal Genome Pre-Alignment Filter for CPUs, GPUs, and FPGAs

Motivation: We introduce SneakySnake, a highly parallel and highly accurate pre-alignment filter that remarkably reduces the need for computationally costly sequence alignment. The key idea of SneakySnake is to reduce the approximate string matching (ASM) problem to the single net routing (SNR) problem in VLSI chip layout. In the SNR problem, we are interested in finding the optimal path that connects two terminals with the least routing cost on a special grid layout that contains obstacles. The SneakySnake algorithm quickly solves the SNR problem and uses the found optimal path to decide whether or not performing sequence alignment is necessary. Reducing the ASM problem into SNR also makes SneakySnake efficient to implement on CPUs, GPUs, and FPGAs. Results: SneakySnake significantly improves the accuracy of pre-alignment filtering by up to four orders of magnitude compared to the state-of-the-art pre-alignment filters, Shouji, GateKeeper, and SHD. For short sequences, SneakySnake accelerates Edlib (state-of-the-art implementation of Myers's bit-vector algorithm) and Parasail (state-of-the-art sequence aligner with a configurable scoring function), by up to 37.7x and 43.9x (>12x on average), respectively, with its CPU implementation, and by up to 413x and 689x (>400x on average), respectively, with FPGA and GPU acceleration. For long sequences, the CPU implementation of SneakySnake accelerates Parasail and KSW2 (sequence aligner of minimap2) by up to 979x (276.9x on average) and 91.7x (31.7x on average), respectively. As SneakySnake does not replace sequence alignment, users can still obtain all capabilities (e.g., configurable scoring functions) of the aligner of their choice, unlike existing acceleration efforts that sacrifice some aligner capabilities. Availability: https://github.com/CMU-SAFARI/SneakySnake

q-bio.GN↗