Abstract:The hippocampus, a critical brain structure involved in memory processing and various neurodegenerative and psychiatric disorders, comprises three key subregions: the dentate gyrus (DG), Cornu Ammonis 1 (CA1), and Cornu Ammonis 3 (CA3). Accurate segmentation of these subregions from histological tissue images is essential for advancing our understanding of disease mechanisms, developmental dynamics, and therapeutic interventions. However, no existing methods address the automated segmentation of hippocampal subregions from tissue images, particularly from immunohistochemistry (IHC) images. To bridge this gap, we introduce a novel set of four comprehensive murine hippocampal IHC datasets featuring distinct staining modalities: cFos, NeuN, and multiplexed stains combining cFos, NeuN, and either {\Delta}FosB or GAD67, capturing structural, neuronal activity, and plasticity associated information. Additionally, we propose ROIsGAN, a region-guided U-Net-based generative adversarial network tailored for hippocampal subregion segmentation. By leveraging adversarial learning, ROIsGAN enhances boundary delineation and structural detail refinement through a novel region-guided discriminator loss combining Dice and binary cross-entropy loss. Evaluated across DG, CA1, and CA3 subregions, ROIsGAN consistently outperforms conventional segmentation models, achieving performance gains ranging from 1-10% in Dice score and up to 11% in Intersection over Union (IoU), particularly under challenging staining conditions. Our work establishes foundational datasets and methods for automated hippocampal segmentation, enabling scalable, high-precision analysis of tissue images in neuroscience research. Our generated datasets, proposed model as a standalone tool, and its corresponding source code are publicly available at: https://github.com/MehediAzim/ROIsGAN
Abstract:Adversarial noise introduces small perturbations in images, misleading deep learning models into misclassification and significantly impacting recognition accuracy. In this study, we analyzed the effects of Fast Gradient Sign Method (FGSM) adversarial noise on image classification and investigated whether training on specific image features can improve robustness. We hypothesize that while adversarial noise perturbs various regions of an image, edges may remain relatively stable and provide essential structural information for classification. To test this, we conducted a series of experiments using brain tumor and COVID datasets. Initially, we trained the models on clean images and then introduced subtle adversarial perturbations, which caused deep learning models to significantly misclassify the images. Retraining on a combination of clean and noisy images led to improved performance. To evaluate the robustness of the edge features, we extracted edges from the original/clean images and trained the models exclusively on edge-based representations. When noise was introduced to the images, the edge-based models demonstrated greater resilience to adversarial attacks compared to those trained on the original or clean images. These results suggest that while adversarial noise is able to exploit complex non-edge regions significantly more than edges, the improvement in the accuracy after retraining is marginally more in the original data as compared to the edges. Thus, leveraging edge-based learning can improve the resilience of deep learning models against adversarial perturbations.
Abstract:The human genome encodes a family of editing enzymes known as APOBEC3 (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3). Several family members, such as APO-BEC3G, APOBEC3F, and APOBEC3H haplotype II, exhibit activity against viruses such as HIV. These enzymes induce C-to-U mutations in the negative strand of viral genomes, resulting in multiple G-to-A changes, commonly referred to as 'hypermutation.' Mutations catalyzed by these enzymes are sequence context-dependent in the HIV genome; for instance, APOBEC3G preferen-tially mutates G within GG, TGG, and TGGG contexts, while other members mutate G within GA, TGA, and TGAA contexts. However, the same sequence context has not been explored in relation to these enzymes and HBV. In this study, our objective is to identify the mutational footprint of APOBEC3 enzymes in the HBV genome. To achieve this, we employ a multivariable data analytics technique to investigate motif preferences and potential sequence hierarchies of mutation by APOBEC3 enzymes using full genome HBV sequences from a diverse range of naturally infected patients. This approach allows us to distinguish between normal and hypermutated sequences based on the representation of mono- to tetra-nucleotide motifs. Additionally, we aim to identify motifs associated with hypermutation induced by different APOBEC3 enzymes in HBV genomes. Our analyses reveal that either APOBEC3 enzymes are not active against HBV, or the induction of G-to-A mutations by these enzymes is not sequence context-dependent in the HBV genome.
Abstract:In recent years, Reinforcement Learning (RL) has emerged as a powerful tool for solving a wide range of problems, including decision-making and genomics. The exponential growth of raw genomic data over the past two decades has exceeded the capacity of manual analysis, leading to a growing interest in automatic data analysis and processing. RL algorithms are capable of learning from experience with minimal human supervision, making them well-suited for genomic data analysis and interpretation. One of the key benefits of using RL is the reduced cost associated with collecting labeled training data, which is required for supervised learning. While there have been numerous studies examining the applications of Machine Learning (ML) in genomics, this survey focuses exclusively on the use of RL in various genomics research fields, including gene regulatory networks (GRNs), genome assembly, and sequence alignment. We present a comprehensive technical overview of existing studies on the application of RL in genomics, highlighting the strengths and limitations of these approaches. We then discuss potential research directions that are worthy of future exploration, including the development of more sophisticated reward functions as RL heavily depends on the accuracy of the reward function, the integration of RL with other machine learning techniques, and the application of RL to new and emerging areas in genomics research. Finally, we present our findings and conclude by summarizing the current state of the field and the future outlook for RL in genomics.