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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 significancemore »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. 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×more »higher energy efficiency than Piggyback.« less
    Free, publicly-accessible full text available July 10, 2023
  3. 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.
    Free, publicly-accessible full text available June 6, 2023
  4. 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.
    Free, publicly-accessible full text available March 31, 2023
  5. Leveraging the ReRAM crossbar-based In-Memory-Computing (IMC) to accelerate single task DNN inference has been widely studied. However, using the ReRAM crossbar for continual learning has not been explored yet. In this work, we propose XST, a novel crossbar column-wise sparse training framework for continual learning. XST significantly reduces the training cost and saves inference energy. More importantly, it is friendly to existing crossbar-based convolution engine with almost no hardware overhead. Compared with the state-of-the-art CPG method, the experiments show that XST's accuracy achieves 4.95 % higher accuracy. Furthermore, XST demonstrates ~5.59 × training speedup and 1.5 × inference energy-saving.
    Free, publicly-accessible full text available March 14, 2023
  6. Recently, utilizing ReRAM crossbar array to accelerate DNN inference on single task has been widely studied. However, using the crossbar array for multiple task adaption has not been well explored. In this paper, for the first time, we propose XBM, a novel crossbar column-wise binary mask learning method for multiple task adaption in ReRAM crossbar DNN accelerator. XBM leverages the mask-based learning algorithm's benefit to avoid catastrophic forgetting to learn a task-specific mask for each new task. With our hardware-aware design innovation, the required masking operation to adapt for a new task could be easily implemented in existing crossbar based convolution engine with minimal hardware/ memory overhead and, more importantly, no need of power hungry cell re-programming, unlike prior works. The extensive experimental results show that compared with state-of-the-art multiple task adaption methods, XBM keeps the similar accuracy on new tasks while only requires 1.4% mask memory size compared with popular piggyback. Moreover, the elimination of cell re-programming or tuning saves up to 40% energy during new task adaption.
    Free, publicly-accessible full text available January 17, 2023
  7. Recently, in-DRAM computing is becoming one promising technique to address the notorious ‘memory-wall’ issue for big data processing. In this work, for the first time, we propose a novel ‘Min/Max-in-memory’ algorithm based on iterative XNOR bit-wise comparison, which supports parallel inmemory searching for minimum and maximum of bulk data stored in DRAM as unsigned & signed integers, fixed-point and floating numbers. We then develop a new processing-in-DRAM architecture, called Max-PIM, that supports complete bit-wise Boolean logic and beyond. Differentiating from prior works, Max-PIM is optimized with one-cycle fast XNOR logicin-DRAM operation and in-memory data transpose, which are heavily used and keys to accelerate the proposed Min/Max-in-memory algorithm efficiently. Extensive experiments of utilizing Max-PIM in big data sorting and graph processing applications show that it could speed up ~ 50X and ~ 1000X than GPU and CPU, while only consuming 10% and 1% energy, respectively. Moreover, comparing with recent representative In-DRAM computing platforms, i.e., Ambit [1], DRISA [2], our design could speed up ~ 3X - 10X.
    Free, publicly-accessible full text available December 5, 2022
  8. Processing-in-memory (PIM) architecture has been considered as a promising solution for the “memory-wall” issue in many data-intensive applications, especially in bioinformatics. Recent works of developing PIM for genome alignment and assembling have achieved tremendous improvement, while another important genome analysis - mRNA quantification has not been explored. Efficient and accurate mRNA quantification is a crucial step for molecular signature identification, disease outcome prediction and drug development. In this paper, for the first time, we propose a SOT-MRAM based PIM platform, named PIM-Quantifier, for efficient mRNA quantification. A PIM-friendly alignment-free quantification algorithm is first proposed. Then, we present the optimized PIM architecture/circuit designs and mapping method to efficiently accelerate mRNA quantification. Extensive experiments show that PIM-Quantifier significantly improves mRNA quantification performance than CPU and recent other PIM platforms in efficiency defined as throughput/power.
    Free, publicly-accessible full text available December 5, 2022
  9. Microbes and viruses are known to alter host transcriptomes by means of infection. In light of recent challenges posed by the COVID-19 pandemic, a deeper understanding of the disease at the transcriptome level is needed. However, research about transcriptome reprogramming by post-transcriptional regulation is very limited. In this study, computational methods developed by our lab were applied to RNA-seq data to detect transcript variants (i.e., alternative splicing (AS) and alternative polyadenylation (APA) events). The RNA-seq data were obtained from a publicly available source, and they consist of mock-treated and SARS-CoV-2 infected (COVID-19) lung alveolar (A549) cells. Data analysis results show that more AS events are found in SARS-CoV-2 infected cells than in mock-treated cells, whereas fewer APA events are detected in SARS-CoV-2 infected cells. A combination of conventional differential gene expression analysis and transcript variants analysis revealed that most of the genes with transcript variants are not differentially expressed. This indicates that no strong correlation exists between differential gene expression and the AS/APA events in the mock-treated or SARS-CoV-2 infected samples. These genes with transcript variants can be applied as another layer of molecular signatures for COVID-19 studies. In addition, the transcript variants are enriched in important biological pathways thatmore »were not detected in the studies that only focused on differential gene expression analysis. Therefore, the pathways may lead to new molecular mechanisms of SARS-CoV-2 pathogenesis.« less
  10. Processing-in-memory (PIM) has raised as a viable solution for the memory wall crisis and has attracted great interest in accelerating computationally intensive AI applications ranging from filtering to complex neural networks. In this paper, we try to take advantage of both PIM and the residue number system (RNS) as an alternative for the conventional binary number representation to accelerate multiplication-and-accumulations (MACs), primary operations of target applications. The PIM architecture utilizes the maximum internal bandwidth of memory chips to realize a local and parallel computation to eliminates the off-chip data transfer. Moreover, RNS limits inter-digit carry propagation by performing arithmetic operations on small residues independently and in parallel. Thus, we develop a PIM-RNS, entitled PRIMS, and analyze the potential of intertwining PIM architecture with the inherent parallelism of the RNS arithmetic to delineate the opportunities and challenges. To this end, we build a comprehensive device-to-architecture evaluation framework to quantitatively study this problem considering the impact of PIM technology for a well-known three-moduli set as a case study.