ClaPIM: Scalable Sequence CLAssification using Processing-In-Memory

DNA sequence classification is a fundamental task in computational biology with vast implications for applications such as disease prevention and drug design. Therefore, fast high-quality sequence classifiers are significantly important. This paper introduces ClaPIM, a scalable DNA sequence classification architecture based on the emerging concept of hybrid in-crossbar and near-crossbar memristive processing-in-memory (PIM). We enable efficient and high-quality classification by uniting the filter and search stages within a single algorithm. Specifically, we propose a custom filtering technique that drastically narrows the search space and a search approach that facilitates approximate string matching through a distance function. ClaPIM is the first PIM architecture for scalable approximate string matching that benefits from the high density of memristive crossbar arrays and the massive computational parallelism of PIM. Compared with Kraken2, a state-of-the-art software classifier, ClaPIM provides significantly higher classification quality (up to 20x improvement in F1 score) and also demonstrates a 1.8x throughput improvement. Compared with EDAM, a recently-proposed SRAM-based accelerator that is restricted to small datasets, we observe both a 30.4x improvement in normalized throughput per area and a 7% increase in classification precision

FASTA: Revisiting Fully Associative Memories in Computer Microarchitecture

Associative access is widely used in fundamental microarchitectural components, such as caches and TLBs. However, associative (or content addressable) memories (CAMs) have been traditionally considered too large, too energy-hungry, and not scalable, and therefore, have limited use in modern computer microarchitecture. This work revisits these presumptions and proposes an energy-efficient fully-associative tag array (FASTA) architecture, based on a novel complementary CAM (CCAM) bitcell. CCAM offers a full CMOS solution for CAM, removing the need for time- and energy-consuming precharge and combining the speed of NOR CAM and low energy consumption of NAND CAM. While providing better performance and energy consumption, CCAM features a larger area compared to state-of-the-art CAM designs. We further show how FASTA can be used to construct a novel aliasing-free, energy-efficient, Very-Many-Way Associative (VMWA) cache. Circuit-level simulations using 16 nm FinFET technology show that a 128 kB FASTA-based 256-way 8-set associative cache is 28% faster and consumes 88% less energy-per-access than a same sized 8-way (256-set) SRAM based cache, while also providing aliasing-free operation. System-level evaluation performed on the Sniper simulator shows that the VMWA cache exhibits lower Misses Per Kilo Instructions (MPKI) for the majority of benchmarks. Specifically, the 256-way associative cache achieves 17.3%, 11.5%, and 1.2% lower average MPKI for L1, L2, and L3 caches, respectively, compared to a 16-way associative cache. The average IPC improvement for L1, L2, and L3 caches are 1.6%, 1.4%, and 0.2%, respectively

Impaired Reorganization of Centrosome Structure Underlies Human Infantile Dilated Cardiomyopathy

Background: During cardiomyocyte maturation, the centrosome, which functions as a microtubule organizing center in cardiomyocytes, undergoes dramatic structural reorganization where its components reorganize from being localized at the centriole to the nuclear envelope. This developmentally programmed process, referred to as centrosome reduction, has been previously associated with cell cycle exit. However, understanding of how this process influences cardiomyocyte cell biology, and whether its disruption results in human cardiac disease, remains unknown. We studied this phenomenon in an infant with a rare case of infantile dilated cardiomyopathy (iDCM) who presented with left ventricular ejection fraction of 18% and disrupted sarcomere and mitochondria structure. Methods: We performed an analysis beginning with an infant who presented with a rare case of iDCM. We derived induced pluripotent stem cells from the patient to model iDCM in vitro. We performed whole exome sequencing on the patient and his parents for causal gene analysis. CRISPR/Cas9-mediated gene knockout and correction in vitro were used to confirm whole exome sequencing results. Zebrafish and Drosophila models were used for in vivo validation of the causal gene. Matrigel mattress technology and single-cell RNA sequencing were used to characterize iDCM cardiomyocytes further. Results: Whole exome sequencing and CRISPR/Cas9 gene knockout/correction identified RTTN, the gene encoding the centrosomal protein RTTN (rotatin), as the causal gene underlying the patient's condition, representing the first time a centrosome defect has been implicated in a nonsyndromic dilated cardiomyopathy. Genetic knockdowns in zebrafish and Drosophila confirmed an evolutionarily conserved requirement of RTTN for cardiac structure and function. Single-cell RNA sequencing of iDCM cardiomyocytes showed impaired maturation of iDCM cardiomyocytes, which underlie the observed cardiomyocyte structural and functional deficits. We also observed persistent localization of the centrosome at the centriole, contrasting with expected programmed perinuclear reorganization, which led to subsequent global microtubule network defects. In addition, we identified a small molecule that restored centrosome reorganization and improved the structure and contractility of iDCM cardiomyocytes. Conclusions: This study is the first to demonstrate a case of human disease caused by a defect in centrosome reduction. We also uncovered a novel role for RTTN in perinatal cardiac development and identified a potential therapeutic strategy for centrosome-related iDCM. Future study aimed at identifying variants in centrosome components may uncover additional contributors to human cardiac disease.</p