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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 that 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. 

(1) Background: A simplistic understanding of the central dogma falls short in correlating the number of genes in the genome to the number of proteins in the proteome. Post-transcriptional alternative splicing contributes to the complexity of the proteome and is critical in understanding gene expression. mRNA-sequencing (RNA-seq) has been widely used to study the transcriptome and provides opportunity to detect alternative splicing events among different biological conditions. Despite the popularity of studying transcriptome variants with RNA-seq, few efficient and user-friendly bioinformatics tools have been developed for the genome-wide detection and visualization of alternative splicing events. (2) Results: We propose AS-Quant, (Alternative Splicing Quantitation), a robust program to identify alternative splicing events from RNA-seq data. We then extended AS-Quant to visualize the splicing events with short-read coverage plots along with complete gene annotation. The tool works in three major steps: (i) calculate the read coverage of the potential spliced exons and the corresponding gene; (ii) categorize the events into five different categories according to the annotation, and assess the significance of the events between two biological conditions; (iii) generate the short reads coverage plot for user specified splicing events. Our extensive experiments on simulated and real datasets demonstrate that AS-Quant outperforms the other three widely used baselines, SUPPA2, rMATS, and diffSplice for detecting alternative splicing events. Moreover, the significant alternative splicing events identified by AS-Quant between two biological contexts were validated by RT-PCR experiment. (3) Availability: AS-Quant is implemented in Python 3.0. Source code and a comprehensive user’s manual are freely available online. 

Deep convolutional neural network (DNN) has demonstrated phenomenal success and been widely used in many computer vision tasks. However, its enormous model size and high computing complexity prohibits its wide deployment into resource limited embedded system, such as FPGA and mGPU. As the two most widely adopted model compression techniques, weight pruning and quantization compress DNN model through introducing weight sparsity (i.e., forcing partial weights as zeros) and quantizing weights into limited bit-width values, respectively. Although there are works attempting to combine the weight pruning and quantization, we still observe disharmony between weight pruning and quantization, especially when more aggressive compression schemes (e.g., Structured pruning and low bit-width quantization) are used. In this work, taking FPGA as the test computing platform and Processing Elements (PE) as the basic parallel computing unit, we first propose a PE-wise structured pruning scheme, which introduces weight sparsification with considering of the architecture of PE. In addition, we integrate it with an optimized weight ternarization approach which quantizes weights into ternary values ({-1,0,+1}), thus converting the dominant convolution operations in DNN from multiplication-and-accumulation (MAC) to addition-only, as well as compressing the original model (from 32-bit floating point to 2-bit ternary representation) by at least 16 times. Then, we investigate and solve the coexistence issue between PE-wise Structured pruning and ternarization, through proposing a Weight Penalty Clipping (WPC) technique with self-adapting threshold. Our experiment shows that the fusion of our proposed techniques can achieve the best state-of-the-art ∼21× PE-wise structured compression rate with merely 1.74%/0.94% (top-1/top-5) accuracy degradation of ResNet-18 on ImageNet dataset. 

With the success of deep neural networks (DNN), many recent works have been focusing on developing hardware accelerator for power and resource-limited embedded system via model compression techniques, such as quantization, pruning, low-rank approximation, etc. However, almost all existing DNN structure is fixed after deployment, which lacks runtime adaptive DNN structure to adapt to its dynamic hardware resource, power budget, throughput requirement, as well as dynamic workload. Correspondingly, there is no runtime adaptive hardware platform to support dynamic DNN structure. To address this problem, we first propose a dynamic channel-adaptive deep neural network (CA-DNN) which can adjust the involved convolution channel (i.e. model size, computing load) at run-time (i.e. at inference stage without retraining) to dynamically trade off between power, speed, computing load and accuracy. Further, we utilize knowledge distillation method to optimize the model and quantize the model to 8-bits and 16-bits, respectively, for hardware friendly mapping. We test the proposed model on CIFAR-10 and ImageNet dataset by using ResNet. Comparing with the same model size of individual model, our CA-DNN achieves better accuracy. Moreover, as far as we know, we are the first to propose a Processing-in-Memory accelerator for such adaptive neural networks structure based on Spin Orbit Torque Magnetic Random Access Memory(SOT-MRAM) computational adaptive sub-arrays. Then, we comprehensively analyze the trade-off of the model with different channel-width between the accuracy and the hardware parameters, eg., energy, memory, and area overhead. 

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 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 provides a means to regulate gene expression at the post-transcriptional level and is known to promote translation. 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. 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. The performance of APA-Scan was validated by qPCR. 

Abstract Motivation Detecting cancer gene expression and transcriptome changes with mRNA-sequencing (RNA-Seq) or array-based data are important for understanding the molecular mechanisms underlying carcinogenesis and cellular events during cancer progression. In previous studies, the differentially expressed genes were detected across patients in one cancer type. These studies ignored the role of mRNA expression changes in driving tumorigenic mechanisms that are either universal or specific in different tumor types. To address the problem, we introduce two network-based multi-task learning frameworks, NetML and NetSML, to discover common differentially expressed genes shared across different cancer types as well as differentially expressed genes specific to each cancer type. The proposed frameworks consider the common latent gene co-expression modules and gene-sample biclusters underlying the multiple cancer datasets to learn the knowledge crossing different tumor types. Results Large-scale experiments on simulations and real cancer high-throughput datasets validate that the proposed network-based multi-task learning frameworks perform better sample classification compared with the models without the knowledge sharing across different cancer types. The common and cancer specific molecular signatures detected by multi-task learning frameworks on TCGA ovarian cancer, breast cancer, and prostate cancer datasets are correlated with the known marker genes and enriched in cancer relevant KEGG pathways and Gene Ontology terms. Availability and Implementation Source code is available at: https://github.com/compbiolabucf/NetML Supplementary information Supplementary data are available at Bioinformatics 

In this paper, we propose ReDRAM, as a reconfigurable DRAM-based processing-in-memory (PIM) accelerator, which transforms current DRAM architecture to massively parallel computational units exploiting the high internal bandwidth of modern memory chips. ReDRAM uses the analog operation of DRAM sub-arrays and elevates it to implement a full set of 1- and 2-input bulk bit-wise operations (NOT, (N)AND, (N)OR, and even X(N)OR) between operands stored in the same bit-line, based on a new dual-row activation mechanism with a modest change to peripheral circuits such sense amplifiers. ReDRAM can be leveraged to greatly reduce energy consumption and latency of complex in-DRAM logic computations relying on state-of-the-art mechanisms based on triple-row activation, dual-contact cells, row initialization, NOR style, etc. The extensive circuit-architecture simulations show that ReDRAM achieves on average 54× and 7.1× higher throughput for performing bulk bit-wise operations compared with CPU and GPU, respectively. Besides, ReDRAM outperforms recent processing-in-DRAM platforms with up to 3.7× better performance.