Multi-Omics Integration for Liver Cancer Using Regression Analysis.

Genetic biomarkers have played a pivotal role in the classification, prognostication, and guidance of clinical cancer therapies. Large-scale and multi-dimensional analyses of entire cancer genomes, as exemplified by projects like The Cancer Genome Atlas (TCGA), have yielded an extensive repository of data that holds the potential to unveil the underlying biology of these malignancies. Mutations stand out as the principal catalysts of cellular transformation. Nonetheless, other global genomic processes, such as alterations in gene expression and chromosomal re-arrangements, also play crucial roles in conferring cellular immortality. The incorporation of multi-omics data specific to cancer has demonstrated the capacity to enhance our comprehension of the molecular mechanisms underpinning carcinogenesis. This report elucidates how the integration of comprehensive data on methylation, gene expression, and copy number variations can effectively facilitate the unsupervised clustering of cancer samples. We have identified regressors that can effectively classify tumor and normal samples with an optimal integration of RNA sequencing, DNA methylation, and copy number variation while also achieving significant p-values. Further, these regressors were trained using linear and logistic regression with k-means clustering. For comparison, we employed autoencoder- and stacking-based omics integration and computed silhouette scores to evaluate the clusters. The proof of concept is illustrated using liver cancer data. Our analysis serves to underscore the feasibility of unsupervised cancer classification by considering genetic markers beyond mutations, thereby emphasizing the clinical relevance of additional global cellular parameters that contribute to the transformative process in cells. This work is clinically relevant because changes in gene expression and genomic re-arrangements have been shown to be signatures of cellular transformation across cancers, as well as in liver cancers.

Performance analysis of data resampling on class imbalance and classification techniques on multi-omics data for cancer classification.

Cancer, in any of its forms, remains a significant public health concern worldwide. Advances in early detection and treatment could lead to a decline in the overall death rate from cancer in recent decades. Therefore, tumor prediction and classification play an important role in fighting cancer. This study built computational models for a joint analysis of RNA seq, copy number variation (CNV), and DNA methylation to classify normal and tumor samples across liver cancer, breast cancer, and colon adenocarcinoma from The Cancer Genome Atlas (TCGA) dataset. Total of 18 machine learning methods were evaluated based on the AUC, precision, recall, and F-measure. Besides, five techniques were compared to ameliorate problems of class imbalance in the cancer datasets. Synthetic Minority Oversampling Technique (SMOTE) demonstrated the best performance. The results indicate that the model applying Stochastic Gradient Descent (SGD) for learning binary class SVM with hinge loss has the highest classification results on liver cancer and breast cancer datasets, with accuracy over 99% and AUC greater than or equal to 0.999. For colon adenocarcinoma dataset, both SGD and Sequential Minimal Optimization (SMO) that implements John Platt's sequential minimal optimization algorithm for training a support vector machine shows an outstanding classification performance with accuracy of 100%, AUC, precision, recall, and F-measure all at 1.000.

Reinforcement-Learning-Based Localization of Hippocampus for Alzheimer's Disease Detection.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily impacting memory and cognitive functions. The hippocampus serves as a key biomarker associated with AD. In this study, we present an end-to-end automated approach for AD detection by introducing a reinforcement-learning-based technique to localize the hippocampus within structural MRI images. Subsequently, this localized hippocampus serves as input for a deep convolutional neural network for AD classification. We model the agent-environment interaction using a Deep Q-Network (DQN), encompassing both a convolutional Target Net and Policy Net. Furthermore, we introduce an integrated loss function that combines cross-entropy and contrastive loss to effectively train the classifier model. Our approach leverages a single optimal slice extracted from each subject's 3D sMRI, thereby reducing computational complexity while maintaining performance comparable to volumetric data analysis methods. To evaluate the effectiveness of our proposed localization and classification framework, we compare its performance to the results achieved by supervised models directly trained on ground truth hippocampal regions as input. The proposed approach demonstrates promising performance in terms of classification accuracy, F1-score, precision, and recall. It achieves an F1-score within an error margin of 3.7% and 1.1% and an accuracy within an error margin of 6.6% and 1.6% when compared to the supervised models trained directly on ground truth masks, all while achieving the highest recall score.

Constructing gene similarity networks using co-occurrence probabilities.

Gene similarity networks play important role in unraveling the intricate associations within diverse cancer types. Conventionally, gauging the similarity between genes has been approached through experimental methodologies involving chemical and molecular analyses, or through the lens of mathematical techniques. However, in our work, we have pioneered a distinctive mathematical framework, one rooted in the co-occurrence of attribute values and single point mutations, thereby establishing a novel approach for quantifying the dissimilarity or similarity among genes. Central to our approach is the recognition of mutations as key players in the evolutionary trajectory of cancer. Anchored in this understanding, our methodology hinges on the consideration of two categorical attributes: mutation type and nucleotide change. These attributes are pivotal, as they encapsulate the critical variations that can precipitate substantial changes in gene behavior and ultimately influence disease progression. Our study takes on the challenge of formulating similarity measures that are intrinsic to genes' categorical data. Taking into account the co-occurrence probability of attribute values within single point mutations, our innovative mathematical approach surpasses the boundaries of conventional methods. We thereby provide a robust and comprehensive means to assess gene similarity and take a significant step forward in refining the tools available for uncovering the subtle yet impactful associations within the complex realm of gene interactions in cancer.

GraphChrom: A Novel Graph-Based Framework for Cancer Classification Using Chromosomal Rearrangement Endpoints.

Chromosomal rearrangements are generally a consequence of improperly repaired double-strand breaks in DNA. These genomic aberrations can be a driver of cancers. Here, we investigated the use of chromosomal rearrangements for classification of cancer tumors and the effect of inter- and intrachromosomal rearrangements in cancer classification. We used data from the Catalogue of Somatic Mutations in Cancer (COSMIC) for breast, pancreatic, and prostate cancers, for which the COSMIC dataset reports the highest number of chromosomal aberrations. We developed a framework known as GraphChrom for cancer classification. GraphChrom was developed using a graph neural network which models the complex structure of chromosomal aberrations (CA) and provides local connectivity between the aberrations. The proposed framework illustrates three important contributions to the field of cancers. Firstly, it successfully classifies cancer types and subtypes. Secondly, it evolved into a novel data extraction technique which can be used to extract more informative graphs (informative aberrations associated with a sample); and thirdly, it predicts that interCAs (rearrangements between two or more chromosomes) are more effective in cancer prediction than intraCAs (rearrangements within the same chromosome), although intraCAs are three times more likely to occur than intraCAs.

Distribution of copy number variations and rearrangement endpoints in human cancers with a review of literature.

Copy number variations (CNVs) which include deletions, duplications, inversions, translocations, and other forms of chromosomal re-arrangements are common to human cancers. In this report we investigated the pattern of these variations with the goal of understanding whether there exist specific cancer signatures. We used re-arrangement endpoint data deposited on the Catalogue of Somatic Mutations in Cancers (COSMIC) for our analysis. Indeed, we find that human cancers are characterized by specific patterns of chromosome rearrangements endpoints which in turn result in cancer specific CNVs. A review of the literature reveals tissue specific mutations which either drive these CNVs or appear as a consequence of CNVs because they confer an advantage to the cancer cell. We also identify several rearrangement endpoints hotspots that were not previously reported. Our analysis suggests that in addition to local chromosomal architecture, CNVs are driven by the internal cellular or nuclear physiology of each cancer tissue.

A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database.

Gliomas are differentiated into two major disease subtypes, astrocytoma or oligodendroglioma, which are then characterized as either IDH (isocitrate dehydrogenase)-wild type or IDH-mutant due to the dramatic differences in prognosis and overall survival. Here, we investigated the genetic background of IDH1-mutant gliomas using the Catalogue of Somatic Mutations in Cancer (COSMIC) database. In astrocytoma patients, we found that IDH1 is often co-mutated with TP53, ATRX, AMBRA1, PREX1, and NOTCH1, but not CHEK2, EGFR, PTEN, or the zinc finger transcription factor ZNF429. The majority of the mutations observed in these genes were further confirmed to be either drivers or pathogenic by the Cancer-Related Analysis of Variants Toolkit (CRAVAT). Gene expression analysis showed down-regulation of DRG2 and MSN expression, both of which promote cell proliferation and invasion. There was also significant over-expression of genes such as NDRG3 and KCNB1 in IDH1-mutant astrocytoma patients. We conclude that IDH1-mutant glioma is characterized by significant genetic changes that could contribute to a better prognosis in glioma patients.

Segmentation and clustering in brain MRI imaging.

Clustering is a vital task in magnetic resonance imaging (MRI) brain imaging and plays an important role in the reliability of brain disease detection, diagnosis, and effectiveness of the treatment. Clustering is used in processing and analysis of brain images for different tasks, including segmentation of brain regions and tissues (grey matter, white matter, and cerebrospinal fluid) and clustering of the atrophy in different parts of the brain. This paper presents a state-of-the-art review of brain MRI studies that use clustering techniques for different tasks.

Resting state functional magnetic resonance imaging processing techniques in stroke studies.

In recent years, there has been considerable research interest in the study of brain connectivity using the resting state functional magnetic resonance imaging (rsfMRI). Studies have explored the brain networks and connection between different brain regions. These studies have revealed interesting new findings about the brain mapping as well as important new insights in the overall organization of functional communication in the brain network. In this paper, after a general discussion of brain networks and connectivity imaging, the brain connectivity and resting state networks are described with a focus on rsfMRI imaging in stroke studies. Then, techniques for preprocessing of the rsfMRI for stroke patients are reviewed, followed by brain connectivity processing techniques. Recent research on brain connectivity using rsfMRI is reviewed with an emphasis on stroke studies. The authors hope this paper generates further interest in this emerging area of computational neuroscience with potential applications in rehabilitation of stroke patients.

Imaging and machine learning techniques for diagnosis of Alzheimer's disease.

Alzheimer's disease (AD) is a common health problem in elderly people. There has been considerable research toward the diagnosis and early detection of this disease in the past decade. The sensitivity of biomarkers and the accuracy of the detection techniques have been defined to be the key to an accurate diagnosis. This paper presents a state-of-the-art review of the research performed on the diagnosis of AD based on imaging and machine learning techniques. Different segmentation and machine learning techniques used for the diagnosis of AD are reviewed including thresholding, supervised and unsupervised learning, probabilistic techniques, Atlas-based approaches, and fusion of different image modalities. More recent and powerful classification techniques such as the enhanced probabilistic neural network of Ahmadlou and Adeli should be investigated with the goal of improving the diagnosis accuracy. A combination of different image modalities can help improve the diagnosis accuracy rate. Research is needed on the combination of modalities to discover multi-modal biomarkers.