Memory isolation is critical for system reliability, security, and safety. Unfortunately, read disturbance can break memory isolation in modern DRAM chips. For example, RowHammer is awell-studied read-disturb phenomenon where repeatedly opening and closing (i.e., hammering) a DRAM row many times causes bitflips in physically nearby rows. This paper experimentally demonstrates and analyzes another widespread read-disturb phenomenon, RowPress, in real DDR4 DRAM chips. RowPress breaks memory isolation by keeping a DRAM row open for a long period of time, which disturbs physically nearby rows enough to cause bitflips. We show that RowPress amplifies DRAM's vulnerability to read-disturb attacks by significantly reducing the number of row activations needed to induce a bitflip by one to two orders of magnitude under realistic conditions. In extreme cases, RowPress induces bitflips in a DRAM row when an adjacent row is activated only once. Our detailed characterization of 164 real DDR4 DRAM chips shows that RowPress 1) affects chips from all three major DRAM manufacturers, 2) gets worse as DRAM technology scales down to smaller node sizes, and 3) affects a different set of DRAM cells from RowHammer and behaves differently from RowHammer as temperature and access pattern changes. We also show that cells vulnerable to RowPress are very different from cells vulnerable to retention failures. We demonstrate in a real DDR4-based system with RowHammer protection that 1) a user-level program induces bitflips by leveraging RowPress while conventional RowHammer cannot do so, and 2) a memory controller that adaptively keeps the DRAM row open for a longer period of time based on access pattern can facilitate RowPress-based attacks. To prevent bitflips due to RowPress, we describe and analyze four potential mitigation techniques, including a new methodology that adapts existing RowHammer mitigation techniques to also mitigate RowPress with low additional performance overhead. We evaluate this methodology and demonstrate that it is effective on a variety of workloads. We open source all our code and data to facilitate future research on RowPress.

Summary: 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 (i) require powerful computational resources that may not be available for portable sequencers or (ii) 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: (i) read mapping, (ii) relative abundance estimation, and (iii) 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 (i) $25.8×$ and $3.4×$ better average throughput and (ii) significantly better accuracy for large genomes, respectively. Source code is available at https://github.com/CMU-SAFARI/RawHash.

Pairwise sequence alignment is a very time-consuming step in common bioinformatics pipelines. Speeding up this step requires heuristics, efficient implementations, and/or hardware acceleration. A promising candidate for all of the above is the recently proposed GenASM algorithm. We identify and address three inefficiencies in the GenASM algorithm: it has a high amount of data movement, a large memory footprint, and does some unnecessary work. We propose Scrooge, a fast and memory-frugal genomic sequence aligner. Scrooge includes three novel algorithmic improvements which reduce the data movement, memory footprint, and the number of operations in the GenASM algorithm. We provide efficient open-source implementations of the Scrooge algorithm for CPUs and GPUs, which demonstrate the significant benefits of our algorithmic improvements. For long reads, the CPU version of Scrooge achieves a 20.1 $×$⁠, 1.7 $×$⁠, and 2.1 $×$ speedup over KSW2, Edlib, and a CPU implementation of GenASM, respectively. The GPU version of Scrooge achieves a 4.0 $×$⁠, 80.4 $×$⁠, 6.8 $×$⁠, 12.6 $×$⁠, and 5.9 $×$ speedup over the CPU version of Scrooge, KSW2, Edlib, Darwin-GPU, and a GPU implementation of GenASM, respectively. We estimate an ASIC implementation of Scrooge to use 3.6 $×$ less chip area and 2.1 $×$ less power than a GenASM ASIC while maintaining the same throughput. Further, we systematically analyze the throughput and accuracy behavior of GenASM and Scrooge under various configurations. As the best configuration of Scrooge depends on the computing platform, we make several observations that can help guide future implementations of Scrooge. https://github.com/CMU-SAFARI/Scrooge.

Summary: Raw nanopore signals can be analyzed while they are being generated, a process known as real-time analysis. Real-time analysis of raw signals is essential to utilize the unique features that nanopore sequencing provides, enabling the early stopping of the sequencing of a read or the entire sequencing run based on the analysis. The state-of-the-art mechanism, RawHash, offers the first hash-based efficient and accurate similarity identification between raw signals and a reference genome by quickly matching their hash values. In this work, we introduce RawHash2, which provides major improvements over RawHash, including more sensitive quantization and chaining algorithms, weighted mapping decisions, frequency filters to reduce ambiguous seed hits, minimizers for hash-based sketching, and support for the R10.4 flow cell version and POD5 and SLOW5 file formats. Compared to RawHash, RawHash2 provides better F1 accuracy (on average by 10.57% and up to 20.25%) and better throughput (on average by 4.0× and up to 9.9×) than RawHash. Availability and implementation: RawHash2 is available at https://github.com/CMU-SAFARI/RawHash. We also provide the scripts to fully reproduce our results on our GitHub page.

Basecalling, an essential step in many genome analysis studies, relies on large Deep Neural Network s (DNN s) to achieve high accuracy. Unfortunately, these DNN s are computationally slow and inefficient, leading to considerable delays and resource constraints in the sequence analysis process. A Computation-In-Memory (CIM) architecture using memristors can significantly accelerate the performance of DNN s. However, inherent device non-idealities and architectural limitations of such designs can greatly degrade the basecalling accuracy, which is critical for accurate genome analysis. To facilitate the adoption of memristor-based CIM designs for basecalling, it is important to (1) conduct a comprehensive analysis of potential CIM architectures and (2) develop effective strategies for mitigating the possible adverse effects of inherent device non-idealities and architectural limitations. This paper proposes Swordfish, a novel hardware/software co-design framework that can effectively address the two aforementioned issues. Swordfish incorporates seven circuit and device restrictions or non-idealities from characterized real memristor-based chips. Swordfish leverages various hardware/software co-design solutions to mitigate the basecalling accuracy loss due to such non-idealities. To demonstrate the effectiveness of Swordfish, we take Bonito, the state-of-the-art (i.e., accurate and fast), open-source basecaller as a case study. Our experimental results using Swordfish show that a CIM architecture can realistically accelerate Bonito for a wide range of real datasets by an average of 25.7 ×, with an accuracy loss of 6.01%.

Nanopore sequencers generate raw electrical signals representing the contents of a biological sequence molecule passing through the nanopore. These signals can be analyzed directly, avoiding base-calling entirely. We observe that while existing proposals for raw signal analysis typically do well in all metrics for small genomes ( e.g. , viral genomes), they all perform poorly for large genomes ( e.g. , the human genome). Our goal is to analyze raw nanopore signals in an accurate, fast, and scalable manner. To this end, we propose RawAlign, the first work to integrate fine-grained signal alignment into the state-of-the-art raw signal mapper. To enable accurate, fast, and scalable mapping with alignment, RawAlign implements three algorithmic improvements and hardware acceleration via a vectorized implementation of fine-grained alignment. Together, these significantly reduce the overhead of typically computationally expensive fine-grained alignment. Our extensive evaluations on different use cases and various datasets show RawAlign provides 1) the most accurate mapping for large genomes and 2) and on-par performance compared to RawHash (between 0.80×-1.08×), while achieving better performance than UNCALLED and Sigmap by on average (geo. mean) 2.83× and 2.06×, respectively. Availability: https://github.com/CMU-SAFARI/RawAlign.