His current research interests broadly span bioinformatics and computer architecture topics, including accurately and quickly identifying sequence similarities, hardware/software co-design for accelerating bioinformatics applications and genomic data analysis, correcting sequencing errors, and developing computational tools for gene editing. He is generally interested in developing new algorithms and architectures for bioinformatics applications to enable fast and accurate genome analysis.
Selected publications
bioRxiv
Can Firtina, Nika Mansouri Ghiasi, Joel Lindegger, Gagandeep Singh, Meryem Banu Cavlak, Haiyu Mao, and Onur Mutlu,
Nanopore sequencers generate electrical raw signals in real-time while sequencing long genomic strands. These raw signals can be analyzed as they are generated, providing an opportunity for real-time genome analysis. An important feature of nanopore sequencing, Read Until, can eject strands from sequencers without fully sequencing them, which provides opportunities to computationally reduce the sequencing time and cost. However, existing works utilizing Read Until either 1) require powerful computational resources that may not be available for portable sequencers or 2) lack scalability for large genomes, rendering them inaccurate or ineffective. We propose RawHash, the first mechanism that can accurately and efficiently perform real-time analysis of nanopore raw signals for large genomes using a hash-based similarity search. To enable this, RawHash ensures the signals corresponding to the same DNA content lead to the same hash value, regardless of the slight variations in these signals. RawHash achieves an accurate hash-based similarity search via an effective quantization of the raw signals such that signals corresponding to the same DNA content have the same quantized value and, subsequently, the same hash value. We evaluate RawHash on three applications: 1) read mapping, 2) relative abundance estimation, and 3) contamination analysis. Our evaluations show that RawHash is the only tool that can provide high accuracy and high throughput for analyzing large genomes in real-time. When compared to the state-of-the-art techniques, UNCALLED and Sigmap, RawHash provides 1) 25.8x and 3.4x better average throughput and 2) an average speedup of 32.1x and 2.1x in the mapping time, respectively. Source code is available at https://github.com/CMU-SAFARI/RawHash.
@article{firtina_rawhash_2023,title={{RawHash}: {Enabling} {Fast} and {Accurate} {Real}-{Time} {Analysis} of {Raw} {Nanopore} {Signals} for {Large} {Genomes}},doi={10.1101/2023.01.22.525080},journal={bioRxiv},author={Firtina, Can and Ghiasi, Nika Mansouri and Lindegger, Joel and Singh, Gagandeep and Cavlak, Meryem Banu and Mao, Haiyu and Mutlu, Onur},month={January},year={2023},pages={2023.01.22.525080},}
NARGAB
Can Firtina, Jisung Park, Mohammed Alser, Jeremie S Kim, Damla Senol Cali, Taha Shahroodi, Nika Mansouri Ghiasi, Gagandeep Singh, Konstantinos Kanellopoulos, Can Alkan, and Onur Mutlu,
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.
@article{firtina_blend_2023,title={{BLEND}: a fast, memory-efficient and accurate mechanism to find fuzzy seed matches in genome analysis},volume={5},issn={2631-9268},url={https://doi.org/10.1093/nargab/lqad004},doi={10.1093/nargab/lqad004},number={1},urldate={2023-01-23},journal={NAR Genomics and Bioinformatics},author={Firtina, Can and Park, Jisung and Alser, Mohammed and Kim, Jeremie S and Cali, Damla Senol and Shahroodi, Taha and Ghiasi, Nika Mansouri and Singh, Gagandeep and Kanellopoulos, Konstantinos and Alkan, Can and Mutlu, Onur},month={March},year={2023},pages={lqad004},}
Profile hidden Markov models (pHMMs) are widely used in many bioinformatics applications to accurately identify similarities between biological sequences (e.g., DNA or protein sequences). PHMMs use a commonly-adopted and highly-accurate method, called the Baum-Welch algorithm, to calculate these similarities. However, the Baum-Welch algorithm is computationally expensive, and existing works provide either software- or hardware-only solutions for a fixed pHMM design. When we analyze the state-of-the-art works, we find that there is a pressing need for a flexible, high-performant, and energy-efficient hardware-software co-design to efficiently and effectively solve all the major inefficiencies in the Baum-Welch algorithm for pHMMs.
We propose ApHMM, the first flexible acceleration framework that can significantly reduce computational and energy overheads of the Baum-Welch algorithm for pHMMs. ApHMM leverages hardware-software co-design to solve the major inefficiencies in the Baum-Welch algorithm by 1) designing a flexible hardware to support different pHMMs designs, 2) exploiting the predictable data dependency pattern in an on-chip memory with memoization techniques, 3) quickly eliminating negligible computations with a hardware-based filter, and 4) minimizing the redundant computations. We implement our 1) hardware-software optimizations on a specialized hardware and 2) software optimizations for GPUs to provide the first flexible Baum-Welch accelerator for pHMMs. ApHMM provides significant speedups of 15.55x-260.03x, 1.83x-5.34x, and 27.97x compared to CPU, GPU, and FPGA implementations of the Baum-Welch algorithm, respectively. ApHMM outperforms the state-of-the-art CPU implementations of three important bioinformatics applications, 1) error correction, 2) protein family search, and 3) multiple sequence alignment, by 1.29x-59.94x, 1.03x-1.75x, and 1.03x-1.95x, respectively.
@article{firtina_aphmm_2022,title={ApHMM: Accelerating Profile Hidden Markov Models for Fast and Energy-Efficient Genome Analysis},journal={arXiv},author={Firtina, Can and Pillai, Kamlesh and Kalsi, Gurpreet S. and Suresh, Bharathwaj and Cali, Damla Senol and Kim, Jeremie and Shahroodi, Taha and Cavlak, Meryem Banu and Lindegger, Joel and Alser, Mohammed and Luna, Juan Gómez and Subramoney, Sreenivas and Mutlu, Onur},year={2022},month={July},doi={10.48550/ARXIV.2207.09765}}
As genome sequencing tools and techniques improve, researchers are able to incrementally assemble more accurate reference genomes, which enable sensitivity in read mapping and downstream analysis such as variant calling. A more sensitive downstream analysis is critical for a better understanding of the genome donor (e.g., health characteristics). Therefore, read sets from sequenced samples should ideally be mapped to the latest available reference genome that represents the most relevant population. Unfortunately, the increasingly large amount of available genomic data makes it prohibitively expensive to fully re-map each read set to its respective reference genome every time the reference is updated. There are several tools that attempt to accelerate the process of updating a read data set from one reference to another (i.e., remapping) by 1) identifying regions that appear similarly between two references and 2) updating the mapping location of reads that map to any of the identified regions in the old reference to the corresponding similar region in the new reference. The main drawback of existing approaches is that if a read maps to a region in the old reference that does not appear with a reasonable degree of similarity in the new reference, the read cannot be remapped. We find that, as a result of this drawback, a significant portion of annotations (i.e., coding regions in a genome) are lost when using state-of-the-art remapping tools. To address this major limitation in existing tools, we propose AirLift, a fast and comprehensive technique for remapping alignments from one genome to another. Compared to the state-of-the-art method for remapping reads (i.e., full mapping), AirLift reduces 1) the number of reads (out of the entire read set) that need to be fully mapped to the new reference by up to 99.99% and 2) the overall execution time to remap read sets between two reference genome versions by 6.7×, 6.6×, and 2.8× for large (human), medium (C. elegans), and small (yeast) reference genomes, respectively. We validate our remapping results with GATK and find that AirLift provides similar accuracy in identifying ground truth SNP and INDEL variants as the baseline of fully mapping a read set.Code Availability AirLift source code and readme describing how to reproduce our results are available at https://github.com/CMU-SAFARI/AirLift.Competing Interest StatementThe authors have declared no competing interest.
@article{kim_airlift_2021,title={{AirLift}: {A} {Fast} and {Comprehensive} {Technique} for {Remapping} {Alignments} between {Reference} {Genomes}},doi={10.1101/2021.02.16.431517},journal={bioRxiv},author={Kim, Jeremie S. and Firtina, Can and Cavlak, Meryem Banu and Cali, Damla Senol and Hajinazar, Nastaran and Alser, Mohammed and Alkan, Can and Mutlu, Onur},month=jan,year={2021},pages={2021.02.16.431517},}
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 technology-dependency 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.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 (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. Source code is available at https://github.com/CMU-SAFARI/Apollo. Supplementary data are available at Bioinformatics online.
@article{firtina_apollo_2020,title={Apollo: a sequencing-technology-independent, scalable and accurate assembly polishing algorithm},volume={36},issn={1367-4803},url={https://doi.org/10.1093/bioinformatics/btaa179},doi={10.1093/bioinformatics/btaa179},number={12},journal={Bioinformatics},author={Firtina, Can and Kim, Jeremie S. and Alser, Mohammed and Senol Cali, Damla and Cicek, A Ercument and Alkan, Can and Mutlu, Onur},month={June},year={2020},pages={3669--3679},}