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Alternative cleavage and polyadenylation within introns (intronic APA) generate shorter mRNA isoforms; however, their physiological significance remains elusive. In this study, we developed a comprehensive workflow to analyze intronic APA profiles using the mammalian target of rapamycin (mTOR)-regulated transcriptome as a model system. Our investigation revealed two contrasting effects within the transcriptome in response to fluctuations in cellular mTOR activity: an increase in intronic APA for a subset of genes and a decrease for another subset of genes. The application of this workflow to RNA-seq data from The Cancer Genome Atlas demonstrated that this dichotomous intronic APA pattern is a consistent feature in transcriptomes across both normal tissues and various cancer types. Notably, our analyses of protein length changes resulting from intronic APA events revealed two distinct phenomena in proteome programming: a loss of functional domains due to significant changes in protein length or minimal alterations in C- terminal protein sequences within unstructured regions. Focusing on conserved intronic APA events across 10 different cancer types highlighted the prevalence of the latter cases in cancer transcriptomes, whereas the former cases were relatively enriched in normal tissue transcriptomes. These observations suggest potential, yet distinct, roles for intronic APA events during pathogenic processes and emphasize the abundance of protein isoforms with similar lengths in the cancer proteome. Furthermore, our investigation into the isoform-specific functions of JMJD6 intronic APA events supported the hypothesis that alterations in unstructured C-terminal protein regions lead to functional differences. Collectively, our findings underscore intronic APA events as a discrete molecular signature present in both normal tissues and cancer transcriptomes, highlighting the contribution of APA to the multifaceted functionality of the cancer proteome.more » « lessFree, publicly-accessible full text available October 1, 2025
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This work presents the first resistive random access memory (RRAM)-based compute-in-memory (CIM) macro design tailored for genome processing. We analyze and demonstrate two key types of genome processing applications using our developed CIM chip prototype: the state-of-the-art (SOTA) burrows–wheeler transform (BWT)-based DNA short- read alignment and alignment-free mRNA quantification. Our CIM macro is designed and optimized to support the major functions essential to these algorithms, e.g., parallel XNOR operations, count, addition, and parallel bit-wise and operations. The proposed CIM macro prototype is fabricated with monolithic integration of HfO2 RRAM and 65-nm CMOS, achieving 2.07 TOPS/W (tera-operations per second per watt) and 2.12 G suffixes/J (suffixes per joule) at 1.0 V, which is the most energy-efficient solution to date for genome processing.more » « lessFree, publicly-accessible full text available July 1, 2025
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Hyb-Learn: A Framework for On-Device Self-Supervised Continual Learning with Hybrid RRAM/SRAM MemoryWhile RRAM crossbar-based In-Memory Computing (IMC) has proven highly effective in accelerating Deep Neural Networks (DNNs) inference, RRAM-based on-device training is less explored due to its high energy consumption of weight re-programming and cells' low endurance problem. Besides, emerging trends indicate a need for on-device continual learning which sequentially acquires knowledge from multiple tasks to enhance user's experiences and eliminate data privacy concerns. However, learning on each new task leads to forgetting prior learned knowledge on prior tasks, which is known as catastrophic forgetting. To address these challenges, we are the first to propose a novel training framework, Hyb-Learn, for enabling on-device continual learning with a hybrid RRAM/SRAM IMC architecture design. Specifically, when training each new arriving task, our approach first partitions the model into two groups based on the proposed task-correlated PE-wise correlation to freeze or re-training, and correspondingly mapping to RRAM and SRAM, respectively. In practice, the RRAM stores frozen weights with strong task correlation to prior tasks to eliminate the high cost of weight reprogramming issue of RRAM, while the SRAM stores the remaining weights that will be updated. Furthermore, to maximize the freezing ratio for improving training efficiency while maintaining accuracy and mitigating catastrophic forgetting, we incorporate self-supervised learning algorithms that are initialized from a pre-trained model for training each new task.more » « lessFree, publicly-accessible full text available June 23, 2025
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With the prosperous development of Deep Neural Network (DNNs), numerous Process-In-Memory (PIM) designs have emerged to accelerate DNN models with exceptional throughput and energy-efficiency. PIM accelerators based on Non-Volatile Memory (NVM) or volatile memory offer distinct advantages for computational efficiency and performance. NVM based PIM accelerators, demonstrated success in DNN inference, face limitations in on-device learning due to high write energy, latency, and instability. Conversely, fast volatile memories, like SRAM, offer rapid read/write operations for DNN training, but suffer from significant leakage currents and large memory footprints. In this paper, for the first time, we present a fully-digital sparse processing in hybrid NVM-SRAM design, synergistically combines the strengths of NVM and SRAM, tailored for on-device continual learning. Our designed NVM and SRAM based PIM circuit macros could support both storage and processing of N:M structured sparsity pattern, significantly improving the storage and computing efficiency. Exhaustive experiments demonstrate that our hybrid system effectively reduces area and power consumption while maintaining high accuracy, offering a scalable and versatile solution for on-device continual learning.more » « lessFree, publicly-accessible full text available June 23, 2025
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Deep neural networks (DNNs) have experienced unprecedented success in a variety of cognitive tasks due to which there has been a move to deploy DNNs in edge devices. DNNs are usually comprised of multiply-and-accumulate (MAC) operations and are both data and compute intensive. In-memory computing (IMC) methodologies have shown significant energy efficiency and throughput benefits for DNN workloads by reducing data movement and eliminating memory reads. Weight pruning in DNNs can further improve the energy/throughput of DNN hardware through reduced storage and compute. Recent IMC works [1]–[3], [6] have not explored such sparse compression techniques unlike ASIC counterparts to enable storage benefits and compute skipping. A recent work [4] attempted to exploit this by compressing weights using a binary map and a custom compression format. This is sub-optimal because the implementation requires a complex routing mechanism (butterfly routing), additional compute to decode compressed weights and has limited flexibility in supporting different sparse encodings. Fig. 1 illustrates our motivations and the challenges for implementing weight compression in digital IMC designs and the need for a new methodology to enable sparse compute directly on compressed weights. In this work, we present a novel sparsity-integrated IMC (SP-IMC) macro in 28nm CMOS which, for the first time, utilizes three popular sparse compression formats, i.e., coordinate representation (COO), run length encoding (RL) and N:m sparsity [7] all along the matrix column direction with tunable precisions. SP-IMC stores and directly processes the sparse compressed weights in the macro, achieving higher storage density, reduction in re-write operations to the macro and higher overall energy efficiency.more » « lessFree, publicly-accessible full text available April 21, 2025
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Due to the separate memory and computation units in traditional Von-Neumann architecture, massive data transfer dominates the overall computing system’s power and latency, known as the ‘Memory-Wall’ issue. Especially with ever-increasing deep learning-based AI model size and computing complexity, it becomes the bottleneck for state-of-the-art AI computing systems. To address this challenge, In-Memory Computing (IMC) based Neural Network accelerators have been widely investigated to support AI computing within memory. However, most of those works focus only on inference. The on-device training and continual learning have not been well explored yet. In this work, for the first time, we introduce on-device continual learning with STT-assisted-SOT (SAS) Magnetic Random Access Memory (MRAM) based IMC system. On the hardware side, we have fabricated a SAS-MRAM device prototype with 4 Magnetic Tunnel Junctions (MTJ, each at 100nm × 50nm) sharing a common heavy metal layer, achieving significantly improved memory writing and area efficiency compared to traditional SOT-MRAM. Next, we designed fully digital IMC circuits with our SAS-MRAM to support both neural network inference and on-device learning. To enable efficient on-device continual learning for new task data, we present an 8-bit integer (INT8) based continual learning algorithm that utilizes our SAS-MRAM IMC-supported bit-serial digital in-memory convolution operations to train a small parallel reprogramming Network (Rep-Net) while freezing the major backbone model. Extensive studies have been presented based on our fabricated SAS-MRAM device prototype, cross-layer device-circuit benchmarking and simulation, as well as the on-device continual learning system evaluation.more » « lessFree, publicly-accessible full text available February 28, 2025
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In this work, we present an efficient Processing in MRAM-Accelerated De Bruijn Graph-based DNA Assembly platform, named PANDA, based on an optimized and hardware-friendly genome assembly algorithm. PANDA is able to assemble large-scale DNA sequence datasets from all-pair overlaps. We first design a PANDA platform that exploits MRAM as computational memory and converts it to a potent processing unit for genome assembly. PANDA can not only execute efficient bulk bit-wise X(N)OR-based comparison/addition operations heavily required for the genome assembly task but also a full set of 2-/3-input logic operations inside the MRAM chip. We then develop a highly parallel and step-by-step hardware-friendly DNA assembly algorithm for PANDA that only requires the developed in-memory logic operations. The platform is then configured with a novel data partitioning and mapping technique that provides local storage and processing to utilize the algorithm level’s parallelism fully. The cross-layer simulation results demonstrate that PANDA reduces the run time and power by a factor of 18 and 11, respectively, compared with CPU. Moreover, speed-ups of up to 2.5 to 10× can be obtained over other recent processing in-memory platforms to perform the same task, like STT-MRAM, ReRAM, and DRAM.more » « lessFree, publicly-accessible full text available February 2, 2025
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We present a fully digital multiply and accumulate (MAC) in-memory computing (IMC) macro demonstrating one of the fastest flexible precision integer-based MACs to date. The design boasts a new bit-parallel architecture enabled by a 10T bit-cell capable of four AND operations and a decomposed precision data flow that decreases the number of shift–accumulate operations, bringing down the overall adder hardware cost by 1.57× while maintaining 100% utilization for all supported precision. It also employs a carry save adder tree that saves 21% of adder hardware. The 28-nm prototype chip achieves a speed-up of 2.6× , 10.8× , 2.42× , and 3.22× over prior SoTA in 1bW:1bI, 1bW:4bI, 4bW:4bI, and 8bW:8bI MACs, respectively.more » « less