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1. Scalable Multi-Instance Multi-Shape Support Vector Machine for Whole Slide Breast Histopathology

   https://doi.org/10.1109/ICKG55886.2022.00036  

   Seo, Hoon; Brand, Lodewijk; Barco, Lucia Saldana; Wang, Hua (November 2022, 2022 IEEE International Conference on Knowledge Graph (ICKG))

   Histopathological image analysis is critical in cancer diagnosis and treatment. Due to the huge size of histopathological images, most existing works analyze the whole slide pathological image (WSI) as a bag and its patches are considered as instances. However, these approaches are limited to analyzing the patches in a fixed shape, while the malignant lesions can form varied shapes. To address this challenge, we propose the Multi-Instance Multi-Shape Support Vector Machine (MIMSSVM) to analyze the multiple images (instances) jointly where each instance consists of multiple patches in varied shapes. In our approach, we can identify the varied morphologic abnormalities of nuclei shapes from the multiple images. In addition to the multi-instance multi-shape learning capability, we provide an efficient algorithm to optimize the proposed model which scales well to a large number of features. Our experimental results show the proposed MIMSSVM method outperforms the existing SVM and recent deep learning models in histopathological classification. The proposed model also identifies the tissue segments in an image exhibiting an indication of an abnormality which provides utility in the early detection of malignant tumors. 

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2. Network-based multi-task learning models for biomarker selection and cancer outcome prediction

   https://doi.org/10.1093/bioinformatics/btz809  

   Wang, Zhibo; He, Zhezhi; Shah, Milan; Zhang, Teng; Fan, Deliang; Zhang, Wei; Cowen, Lenore (November 2019, Bioinformatics)

   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 

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3. Multi-omics data integration by generative adversarial network

   https://doi.org/10.1093/bioinformatics/btab608  

   Ahmed, Khandakar Tanvir; Sun, Jiao; Cheng, Sze; Yong, Jeongsik; Zhang, Wei (August 2021, Bioinformatics)

   Robinson, Peter (Ed.)

   Abstract Motivation Accurate disease phenotype prediction plays an important role in the treatment of heterogeneous diseases like cancer in the era of precision medicine. With the advent of high throughput technologies, more comprehensive multi-omics data is now available that can effectively link the genotype to phenotype. However, the interactive relation of multi-omics datasets makes it particularly challenging to incorporate different biological layers to discover the coherent biological signatures and predict phenotypic outcomes. In this study, we introduce omicsGAN, a generative adversarial network model to integrate two omics data and their interaction network. The model captures information from the interaction network as well as the two omics datasets and fuse them to generate synthetic data with better predictive signals. Results Large-scale experiments on The Cancer Genome Atlas breast cancer, lung cancer and ovarian cancer datasets validate that (i) the model can effectively integrate two omics data (e.g. mRNA and microRNA expression data) and their interaction network (e.g. microRNA-mRNA interaction network). The synthetic omics data generated by the proposed model has a better performance on cancer outcome classification and patients survival prediction compared to original omics datasets. (ii) The integrity of the interaction network plays a vital role in the generation of synthetic data with higher predictive quality. Using a random interaction network does not allow the framework to learn meaningful information from the omics datasets; therefore, results in synthetic data with weaker predictive signals. Availability and implementation Source code is available at: https://github.com/CompbioLabUCF/omicsGAN. Supplementary information Supplementary data are available at Bioinformatics online. 

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4. AGRN: accurate gene regulatory network inference using ensemble machine learning methods

   https://doi.org/10.1093/bioadv/vbad032  

   Alawad, Duaa Mohammad; Katebi, Ataur; Kabir, Md Wasi; Hoque, Md Tamjidul (January 2023, Bioinformatics Advances)

   Kuijjer, Marieke (Ed.)

   Abstract Motivation Biological processes are regulated by underlying genes and their interactions that form gene regulatory networks (GRNs). Dysregulation of these GRNs can cause complex diseases such as cancer, Alzheimer’s and diabetes. Hence, accurate GRN inference is critical for elucidating gene function, allowing for the faster identification and prioritization of candidate genes for functional investigation. Several statistical and machine learning-based methods have been developed to infer GRNs based on biological and synthetic datasets. Here, we developed a method named AGRN that infers GRNs by employing an ensemble of machine learning algorithms. Results From the idea that a single method may not perform well on all datasets, we calculate the gene importance scores using three machine learning methods—random forest, extra tree and support vector regressors. We calculate the importance scores from Shapley Additive Explanations, a recently published method to explain machine learning models. We have found that the importance scores from Shapley values perform better than the traditional importance scoring methods based on almost all the benchmark datasets. We have analyzed the performance of AGRN using the datasets from the DREAM4 and DREAM5 challenges for GRN inference. The proposed method, AGRN—an ensemble machine learning method with Shapley values, outperforms the existing methods both in the DREAM4 and DREAM5 datasets. With improved accuracy, we believe that AGRN inferred GRNs would enhance our mechanistic understanding of biological processes in health and disease. Availabilityand implementation https://github.com/DuaaAlawad/AGRN. Supplementary information Supplementary data are available at Bioinformatics online. 

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5. Texture-based Deep Learning for Effective Histopathological Cancer Image Classification

   https://doi.org/10.1109/BIBM47256.2019.8983226  

   Tsaku, Nelson Zange; Kosaraju, Sai Chandra; Aqila, Tasmia; Masum, Mohammad; Song, Dae Hyun; Mondal, Ananda M.; Koh, Hyun Min; Kang, Mingon (November 2019, 2019 IEEE International Conference on Bioinformatics and Biomedicine (IEEE BIBM))

   Automatic histopathological Whole Slide Image (WSI) analysis for cancer classification has been highlighted along with the advancements in microscopic imaging techniques, since manual examination and diagnosis with WSIs are time- and cost-consuming. Recently, deep convolutional neural networks have succeeded in histopathological image analysis. However, despite the success of the development, there are still opportunities for further enhancements. In this paper, we propose a novel cancer texture-based deep neural network (CAT-Net) that learns scalable morphological features from histopathological WSIs. The innovation of CAT-Net is twofold: (1) capturing invariant spatial patterns by dilated convolutional layers and (2) improving predictive performance while reducing model complexity. Moreover, CAT-Net can provide discriminative morphological (texture) patterns formed on cancerous regions of histopathological images comparing to normal regions. We elucidated how our proposed method, CAT-Net, captures morphological patterns of interest in hierarchical levels in the model. The proposed method out-performed the current state-of-the-art benchmark methods on accuracy, precision, recall, and F1 score. 

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