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  1. Abstract Background

    The eukaryotic genome is capable of producing multiple isoforms from a gene by alternative polyadenylation (APA) during pre-mRNA processing. APA in the 3′-untranslated region (3′-UTR) of mRNA produces transcripts with shorter or longer 3′-UTR. Often, 3′-UTR serves as a binding platform for microRNAs and RNA-binding proteins, which affect the fate of the mRNA transcript. Thus, 3′-UTR APA is known to modulate translation and provides a mean to regulate gene expression at the post-transcriptional level. Current bioinformatics pipelines have limited capability in profiling 3′-UTR APA events due to incomplete annotations and a low-resolution analyzing power: widely available bioinformatics pipelines do not reference actionable polyadenylation (cleavage) sites but simulate 3′-UTR APA only using RNA-seq read coverage, causing false positive identifications. To overcome these limitations, we developed APA-Scan, a robust program that identifies 3′-UTR APA events and visualizes the RNA-seq short-read coverage with gene annotations.

    Methods

    APA-Scan utilizes either predicted or experimentally validated actionable polyadenylation signals as a reference for polyadenylation sites and calculates the quantity of long and short 3′-UTR transcripts in the RNA-seq data. APA-Scan works in three major steps: (i) calculate the read coverage of the 3′-UTR regions of genes; (ii) identify the potential APA sites and evaluate the significance of the events among two biological conditions; (iii) graphical representation of user specific event with 3′-UTR annotation and read coverage on the 3′-UTR regions. APA-Scan is implemented in Python3. Source code and a comprehensive user’s manual are freely available athttps://github.com/compbiolabucf/APA-Scan.

    Result

    APA-Scan was applied to both simulated and real RNA-seq datasets and compared with two widely used baselines DaPars and APAtrap. In simulation APA-Scan significantly improved the accuracy of 3′-UTR APA identification compared to the other baselines. The performance of APA-Scan was also validated by 3′-end-seq data and qPCR on mouse embryonic fibroblast cells. The experiments confirm that APA-Scan can detect unannotated 3′-UTR APA events and improve genome annotation.

    Conclusion

    APA-Scan is a comprehensive computational pipeline to detect transcriptome-wide 3′-UTR APA events. The pipeline integrates both RNA-seq and 3′-end-seq data information and can efficiently identify the significant events with a high-resolution short reads coverage plots.

     
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  2. 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. 
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    Free, publicly-accessible full text available October 1, 2025
  3. In genomic analysis, the major computation bottle- neck is the memory- and compute-intensive DNA short reads alignment due to memory-wall challenge. This work presents the first Resistive RAM (RRAM) based Compute-in-Memory (CIM) macro design for accelerating state-of-the-art BWT based genome sequencing alignment. Our design could support all the core instructions, i.e., XNOR based match, count, and addition, required by alignment algorithm. The proposed CIM macro implemented in integration of HfO2 RRAM and 65nm CMOS demonstrates the best energy efficiency to date with 2.07 TOPS/W and 2.12G suffixes/J at 1.0V. 
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  4. Channel decoders are key computing modules in wired/wireless communication systems. Recently neural network (NN)-based decoders have shown their promising error-correcting performance because of their end-to-end learning capability. However, compared with the traditional approaches, the emerging neural belief propagation (NBP) solution suffers higher storage and computational complexity, limiting its hardware performance. To address this challenge and develop a channel decoder that can achieve high decoding performance and hardware performance simultaneously, in this paper we take a first step towards exploring SRAM-based in-memory computing for efficient NBP channel decoding. We first analyze the unique sparsity pattern in the NBP processing, and then propose an efficient and fully Digital Sparse In-Memory Matrix vector Multiplier (DSPIMM) computing platform. Extensive experiments demonstrate that our proposed DSPIMM achieves significantly higher energy efficiency and throughput than the state-of-the-art counterparts. 
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  5. Recently, ReRAM crossbar-based deep neural network (DNN) accelerator has been widely investigated. However, most prior works focus on single-task inference due to the high energy consumption of weight reprogramming and ReRAM cells’ low endurance issue. Adapting the ReRAM crossbar-based DNN accelerator for multiple tasks has not been fully explored. In this study, we propose XMA 2 , a novel crossbar-aware learning method with a 2-tier masking technique to efficiently adapt a DNN backbone model deployed in the ReRAM crossbar for new task learning. During the XMA 2 -based multi-task adaption (MTA), the tier-1 ReRAM crossbar-based processing-element- (PE-) wise mask is first learned to identify the most critical PEs to be reprogrammed for essential new features of the new task. Subsequently, the tier-2 crossbar column-wise mask is applied within the rest of the weight-frozen PEs to learn a hardware-friendly and column-wise scaling factor for new task learning without modifying the weight values. With such crossbar-aware design innovations, we could implement the required masking operation in an existing crossbar-based convolution engine with minimal hardware/memory overhead to adapt to a new task. The extensive experimental results show that compared with other state-of-the-art multiple-task adaption methods, XMA 2 achieves the highest accuracy on all popular multi-task learning datasets. 
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  6. We present a generic and programmable Processing-in-SRAM (PSRAM) accelerator chip design based on an 8T-SRAM array to accommodate a complete set of Boolean logic operations (e.g., NOR/NAND/XOR, both 2- and 3-input), majority, and full adder, for the first time, all in a single cycle. PSRAM provides the programmability required for in-memory computing platforms that could be used for various applications such as parallel vector operation, neural networks, and data encryption. The prototype design is implemented in a SRAM macro with size of 16 kb, demonstrating one of the fastest programmable in-memory computing system to date operating at 1.23 GHz. The 65nm prototype chip achieves system-level peak throughput of 1.2 TOPS, and energy-efficiency of 34.98 TOPS/W at 1.2V. 
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  7. ReRAM crossbar array as a high-parallel fast and energy-efficient structure attracts much attention, especially on the acceleration of Deep Neural Network (DNN) inference on one specific task. However, due to the high energy consumption of weight re-programming and the ReRAM cells’ low endurance problem, adapting the crossbar array for multiple tasks has not been well explored. In this paper, we propose XMA, a novel crossbar-aware shift-based mask learning method for multiple task adaption in the ReRAM crossbar DNN accelerator for the first time. XMA leverages the popular mask-based learning algorithm’s benefit to mitigate catastrophic forgetting and learn a task-specific, crossbar column-wise, and shift-based multi-level mask, rather than the most commonly used elementwise binary mask, for each new task based on a frozen backbone model. With our crossbar-aware design innovation, the required masking operation to adapt for a new task could be implemented in an existing crossbar-based convolution engine with minimal hardware/memory overhead and, more importantly, no need for power-hungry cell re-programming, unlike prior works. The extensive experimental results show that, compared with state-of-the art multiple task adaption Piggyback method [1], XMA achieves 3.19% higher accuracy on average, while saving 96.6% memory overhead. Moreover, by eliminating cell re-programming, XMA achieves ∼4.3× higher energy efficiency than Piggyback. 
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  8. In-Memory Computing (IMC) technology has been considered to be a promising approach to solve well-known memory-wall challenge for data intensive applications. In this paper, we are the first to propose MnM, a novel IMC system with innovative architecture/circuit designs for fast and efficient Min/Max searching computation in emerging Spin-Orbit Torque Magnetic Random Access Memory (SOT-MRAM). Our proposed SOT-MRAM based in-memory logic circuits are specially optimized to perform parallel, one-cycle XNOR logic that are heavily used in the Min/Max searching-in-memory algorithm. Our novel in-memory XNOR circuit also has an overhead of just two transistors per row when compared to most prior methodologies which typically use multiple sense amplifiers or complex CMOS logic gates. We also design all other required peripheral circuits for implementing complete Min/Max searching-in-MRAM computation. Our cross-layer comprehensive experiments on Dijkstra's algorithm and other sorting algorithms in real word datasets show that our MnM could achieve significant performance improvement over CPUs, GPUs, and other competing IMC platforms based on RRAM/MRAM/DRAM. 
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  9. Magneto-Electric FET ( MEFET ) is a recently developed post-CMOS FET, which offers intriguing characteristics for high-speed and low-power design in both logic and memory applications. In this article, we present MeF-RAM , a non-volatile cache memory design based on 2-Transistor-1-MEFET ( 2T1M ) memory bit-cell with separate read and write paths. We show that with proper co-design across MEFET device, memory cell circuit, and array architecture, MeF-RAM is a promising candidate for fast non-volatile memory ( NVM ). To evaluate its cache performance in the memory system, we, for the first time, build a device-to-architecture cross-layer evaluation framework to quantitatively analyze and benchmark the MeF-RAM design with other memory technologies, including both volatile memory (i.e., SRAM, eDRAM) and other popular non-volatile emerging memory (i.e., ReRAM, STT-MRAM, and SOT-MRAM). The experiment results for the PARSEC benchmark suite indicate that, as an L2 cache memory, MeF-RAM reduces Energy Area Latency ( EAT ) product on average by ~98% and ~70% compared with typical 6T-SRAM and 2T1R SOT-MRAM counterparts, respectively. 
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