Md Ashad Alam

Biplab Biswas, Nishith Kumar, Md Aminul Hoque et al.

Systematic variation is a common issue in metabolomics data analysis. Therefore, different scaling and normalization techniques are used to preprocess the data for metabolomics data analysis. Although several scaling methods are available in the literature, however, choice of scaling, transformation and/or normalization technique influence the further statistical analysis. It is challenging to choose the appropriate scaling technique for downstream analysis to get accurate results or to make a proper decision. Moreover, the existing scaling techniques are sensitive to outliers or extreme values. To fill the gap, our objective is to introduce a robust scaling approach that is not influenced by outliers as well as provides more accurate results for downstream analysis. Here, we introduced a new weighted scaling approach that is robust against outliers however, where no additional outlier detection/treatment step is needed in data preprocessing and also compared it with the conventional scaling and normalization techniques through artificial and real metabolomics datasets. We evaluated the performance of the proposed method in comparison to the other existing conventional scaling techniques using metabolomics data analysis in both the absence and presence of different percentages of outliers. Results show that in most cases, the proposed scaling technique performs better than the traditional scaling methods in both the absence and presence of outliers. The proposed method improves the further downstream metabolomics analysis. The R function of the proposed robust scaling method is available at https://github.com/nishithkumarpaul/robustScaling/blob/main/wscaling.R

Md Ashad Alam

RKUM is an R package developed for implementing robust kernel-based unsupervised methods. It provides functions for estimating the robust kernel covariance operator (CO) and the robust kernel cross-covariance operator (CCO) using generalized loss functions instead of the conventional quadratic loss. These operators form the foundation of robust kernel learning and enable reliable analysis under contaminated or noisy data conditions. The package includes implementations of robust kernel canonical correlation analysis (Kernel CCA), as well as the influence function (IF) for both standard and multiple kernel CCA frameworks. The influence function quantifies sensitivity and helps detect influential or outlying observations across two-view and multi-view datasets. Experiments using synthesized two-view and multi-view data demonstrate that the IF of the standard kernel CCA effectively identifies outliers, while the robust kernel methods implemented in RKUM exhibit reduced sensitivity to contamination. Overall, RKUM provides an efficient and extensible platform for robust kernel-based analysis in high-dimensional data applications.

Md. Imtyaz Ahmed, Md. Delwar Hossain, Md Mostafizer Rahman et al.

Cancer exhibits diverse and complex phenotypes driven by multifaceted molecular interactions. Recent biomedical research has emphasized the comprehensive study of such diseases by integrating multi-omics datasets (genome, proteome, transcriptome, epigenome). This approach provides an efficient method for identifying genetic variants associated with cancer and offers a deeper understanding of how the disease develops and spreads. However, it is challenging to comprehend complex interactions among the features of multi-omics datasets compared to single omics. In this paper, we analyze lung cancer multi-omics datasets from The Cancer Genome Atlas (TCGA). Using four statistical methods, LIMMA, the T test, Canonical Correlation Analysis (CCA), and the Wilcoxon test, we identified differentially expressed genes across gene expression, DNA methylation, and miRNA expression data. We then integrated these multi-omics data using the Kernel Machine Regression (KMR) approach. Our findings reveal significant interactions among the three omics: gene expression, miRNA expression, and DNA methylation in lung cancer. From our data analysis, we identified 38 genes significantly associated with lung cancer. From our data analysis, we identified 38 genes significantly associated with lung cancer. Among these, eight genes of highest ranking (PDGFRB, PDGFRA, SNAI1, ID1, FGF11, TNXB, ITGB1, ZIC1) were highlighted by rigorous statistical analysis. Furthermore, in silico studies identified three top-ranked potential candidate drugs (Selinexor, Orapred, and Capmatinib) that could play a crucial role in the treatment of lung cancer. These proposed drugs are also supported by the findings of other independent studies, which underscore their potential efficacy in the fight against lung cancer.

Md Selim Reza, Sabrin Afroz, Mostafizer Rahman et al.

Multi-omics data integration is crucial for understanding complex diseases, yet limited sample sizes, noise, and heterogeneity often reduce predictive power. To address these challenges, we introduce Omics-GAN, a Generative Adversarial Network (GAN)-based framework designed to generate high-quality synthetic multi-omics profiles while preserving biological relationships. We evaluated Omics-GAN on three omics types (mRNA, miRNA, and DNA methylation) using the ROSMAP cohort for Alzheimer's disease (AD) and TCGA datasets for colon and liver cancer. A support vector machine (SVM) classifier with repeated 5-fold cross-validation demonstrated that synthetic datasets consistently improved prediction accuracy compared to original omics profiles. The AUC of SVM for mRNA improved from 0.72 to 0.74 in AD, and from 0.68 to 0.72 in liver cancer. Synthetic miRNA enhanced classification in colon cancer from 0.59 to 0.69, while synthetic methylation data improved performance in liver cancer from 0.64 to 0.71. Boxplot analyses confirmed that synthetic data preserved statistical distributions while reducing noise and outliers. Feature selection identified significant genes overlapping with original datasets and revealed additional candidates validated by GO and KEGG enrichment analyses. Finally, molecular docking highlighted potential drug repurposing candidates, including Nilotinib for AD, Atovaquone for liver cancer, and Tecovirimat for colon cancer. Omics-GAN enhances disease prediction, preserves biological fidelity, and accelerates biomarker and drug discovery, offering a scalable strategy for precision medicine applications.

Md Ashad Alam, Md Amanullah

Diabetes mellitus is a chronic metabolic disorder that necessitates novel therapeutic innovations due to its gradual progression and the onset of various metabolic complications. Research indicates that Ficus religiosa is a conventional medicinal plant that generates bioactive phytochemicals with potential antidiabetic properties. The investigation employs ecosystem-based computational approaches utilizing artificial intelligence to investigate and evaluate compounds derived from Ficus religiosa that exhibit antidiabetic properties. A comprehensive computational procedure incorporated machine learning methodologies, molecular docking techniques, and ADMET prediction systems to assess phytochemical efficacy against the significant antidiabetic enzyme dipeptidyl peptidase-4 (DPP-4). DeepBindGCN and the AutoDock software facilitated the investigation of binding interactions via deep learning technology. Flavonoids and alkaloids have emerged as attractive phytochemicals due to their strong binding interactions and advantageous pharmacological effects, as indicated by the study. The introduction of AI accelerated screening procedures and enhanced accuracy rates, demonstrating its efficacy in researching plant-based antidiabetic agents. The scientific foundation now facilitates future experimental validation of natural product therapies tailored for diabetic management.

Md. Mostafizer Rahman, Ariful Islam Shiplu, Yutaka Watanobe et al.

Effectively analyzing the comments to uncover latent intentions holds immense value in making strategic decisions across various domains. However, several challenges hinder the process of sentiment analysis including the lexical diversity exhibited in comments, the presence of long dependencies within the text, encountering unknown symbols and words, and dealing with imbalanced datasets. Moreover, existing sentiment analysis tasks mostly leveraged sequential models to encode the long dependent texts and it requires longer execution time as it processes the text sequentially. In contrast, the Transformer requires less execution time due to its parallel processing nature. In this work, we introduce a novel hybrid deep learning model, RoBERTa-BiLSTM, which combines the Robustly Optimized BERT Pretraining Approach (RoBERTa) with Bidirectional Long Short-Term Memory (BiLSTM) networks. RoBERTa is utilized to generate meaningful word embedding vectors, while BiLSTM effectively captures the contextual semantics of long-dependent texts. The RoBERTa-BiLSTM hybrid model leverages the strengths of both sequential and Transformer models to enhance performance in sentiment analysis. We conducted experiments using datasets from IMDb, Twitter US Airline, and Sentiment140 to evaluate the proposed model against existing state-of-the-art methods. Our experimental findings demonstrate that the RoBERTa-BiLSTM model surpasses baseline models (e.g., BERT, RoBERTa-base, RoBERTa-GRU, and RoBERTa-LSTM), achieving accuracies of 80.74%, 92.36%, and 82.25% on the Twitter US Airline, IMDb, and Sentiment140 datasets, respectively. Additionally, the model achieves F1-scores of 80.73%, 92.35%, and 82.25% on the same datasets, respectively.

Md Ashad Alam, Hui Shen, Hong-Wen Deng

Many statistical machine approaches could ultimately highlight novel features of the etiology of complex diseases by analyzing multi-omics data. However, they are sensitive to some deviations in distribution when the observed samples are potentially contaminated with adversarial corrupted outliers (e.g., a fictional data distribution). Likewise, statistical advances lag in supporting comprehensive data-driven analyses of complex multi-omics data integration. We propose a novel non-linear M-estimator-based approach, "robust kernel machine regression (RobKMR)," to improve the robustness of statistical machine regression and the diversity of fictional data to examine the higher-order composite effect of multi-omics datasets. We address a robust kernel-centered Gram matrix to estimate the model parameters accurately. We also propose a robust score test to assess the marginal and joint Hadamard product of features from multi-omics data. We apply our proposed approach to a multi-omics dataset of osteoporosis (OP) from Caucasian females. Experiments demonstrate that the proposed approach effectively identifies the inter-related risk factors of OP. With solid evidence (p-value = 0.00001), biological validations, network-based analysis, causal inference, and drug repurposing, the selected three triplets ((DKK1, SMTN, DRGX), (MTND5, FASTKD2, CSMD3), (MTND5, COG3, CSMD3)) are significant biomarkers and directly relate to BMD. Overall, the top three selected genes (DKK1, MTND5, FASTKD2) and one gene (SIDT1 at p-value= 0.001) significantly bond with four drugs- Tacrolimus, Ibandronate, Alendronate, and Bazedoxifene out of 30 candidates for drug repurposing in OP. Further, the proposed approach can be applied to any disease model where multi-omics datasets are available.

Md Ashad Alam, Chuan Qiu, Hui Shen et al.

In recent years, a comprehensive study of multi-view datasets (e.g., multi-omics and imaging scans) has been a focus and forefront in biomedical research. State-of-the-art biomedical technologies are enabling us to collect multi-view biomedical datasets for the study of complex diseases. While all the views of data tend to explore complementary information of a disease, multi-view data analysis with complex interactions is challenging for a deeper and holistic understanding of biological systems. In this paper, we propose a novel generalized kernel machine approach to identify higher-order composite effects in multi-view biomedical datasets. This generalized semi-parametric (a mixed-effect linear model) approach includes the marginal and joint Hadamard product of features from different views of data. The proposed kernel machine approach considers multi-view data as predictor variables to allow more thorough and comprehensive modeling of a complex trait. The proposed method can be applied to the study of any disease model, where multi-view datasets are available. We applied our approach to both synthesized datasets and real multi-view datasets from adolescence brain development and osteoporosis study, including an imaging scan dataset and five omics datasets. Our experiments demonstrate that the proposed method can effectively identify higher-order composite effects and suggest that corresponding features (genes, region of interests, and chemical taxonomies) function in a concerted effort. We show that the proposed method is more generalizable than existing ones.

Md. Siraj-Ud-Doula, Md. Ashad Alam

Classification is an important supervised machine learning method, which is necessary and challenging issue for ecological research. It offers a way to classify a dataset into subsets that share common patterns. Notably, there are many classification algorithms to choose from, each making certain assumptions about the data and about how classification should be formed. In this paper, we applied eight machine learning classification algorithms such as Decision Trees, Random Forest, Artificial Neural Network, Support Vector Machine, Linear Discriminant Analysis, k-nearest neighbors, Logistic Regression and Naive Bayes on ecological data. The goal of this study is to compare different machine learning classification algorithms in ecological dataset. In this analysis we have checked the accuracy test among the algorithms. In our study we conclude that Linear Discriminant Analysis and k-nearest neighbors are the best methods among all other methods

Md. Ashad Alam, Mohammad Shahjama, Md. Ferdush Rahman

Identifying significant subsets of the genes, gene shaving is an essential and challenging issue for biomedical research for a huge number of genes and the complex nature of biological networks,. Since positive definite kernel based methods on genomic information can improve the prediction of diseases, in this paper we proposed a new method, "kernel gene shaving (kernel canonical correlation analysis (kernel CCA) based gene shaving). This problem is addressed using the influence function of the kernel CCA. To investigate the performance of the proposed method in a comparison of three popular gene selection methods (T-test, SAM and LIMMA), we were used extensive simulated and real microarray gene expression datasets. The performance measures AUC was computed for each of the methods. The achievement of the proposed method has improved than the three well-known gene selection methods. In real data analysis, the proposed method identified a subsets of $210$ genes out of $2000$ genes. The network of these genes has significantly more interactions than expected, which indicates that they may function in a concerted effort on colon cancer.

Md. Ashad Alam, Hui-Yi Lin, Vince Calhoun et al.

In this study, we tested the interaction effect of multimodal datasets using a novel method called the kernel method for detecting higher order interactions among biologically relevant mulit-view data. Using a semiparametric method on a reproducing kernel Hilbert space (RKHS), we used a standard mixed-effects linear model and derived a score-based variance component statistic that tests for higher order interactions between multi-view data. The proposed method offers an intangible framework for the identification of higher order interaction effects (e.g., three way interaction) between genetics, brain imaging, and epigenetic data. Extensive numerical simulation studies were first conducted to evaluate the performance of this method. Finally, this method was evaluated using data from the Mind Clinical Imaging Consortium (MCIC) including single nucleotide polymorphism (SNP) data, functional magnetic resonance imaging (fMRI) scans, and deoxyribonucleic acid (DNA) methylation data, respectfully, in schizophrenia patients and healthy controls. We treated each gene-derived SNPs, region of interest (ROI) and gene-derived DNA methylation as a single testing unit, which are combined into triplets for evaluation. In addition, cardiovascular disease risk factors such as age, gender, and body mass index were assessed as covariates on hippocampal volume and compared between triplets. Our method identified $13$-triplets ($p$-values $\leq 0.001$) that included $6$ gene-derived SNPs, $10$ ROIs, and $6$ gene-derived DNA methylations that correlated with changes in hippocampal volume, suggesting that these triplets may be important in explaining schizophrenia-related neurodegeneration. With strong evidence ($p$-values $\leq 0.000001$), the triplet ({\bf MAGI2, CRBLCrus1.L, FBXO28}) has the potential to distinguish schizophrenia patients from the healthy control variations.

Md. Ashad Alam, Kenji Fukumizu, Yu-Ping Wang

Many unsupervised kernel methods rely on the estimation of the kernel covariance operator (kernel CO) or kernel cross-covariance operator (kernel CCO). Both kernel CO and kernel CCO are sensitive to contaminated data, even when bounded positive definite kernels are used. To the best of our knowledge, there are few well-founded robust kernel methods for statistical unsupervised learning. In addition, while the influence function (IF) of an estimator can characterize its robustness, asymptotic properties and standard error, the IF of a standard kernel canonical correlation analysis (standard kernel CCA) has not been derived yet. To fill this gap, we first propose a robust kernel covariance operator (robust kernel CO) and a robust kernel cross-covariance operator (robust kernel CCO) based on a generalized loss function instead of the quadratic loss function. Second, we derive the IF for robust kernel CCO and standard kernel CCA. Using the IF of the standard kernel CCA, we can detect influential observations from two sets of data. Finally, we propose a method based on the robust kernel CO and the robust kernel CCO, called {\bf robust kernel CCA}, which is less sensitive to noise than the standard kernel CCA. The introduced principles can also be applied to many other kernel methods involving kernel CO or kernel CCO. Our experiments on synthesized data and imaging genetics analysis demonstrate that the proposed IF of standard kernel CCA can identify outliers. It is also seen that the proposed robust kernel CCA method performs better for ideal and contaminated data than the standard kernel CCA.

Owen Richfield, Md. Ashad Alam, Vince Calhoun et al.

Kernel and Multiple Kernel Canonical Correlation Analysis (CCA) are employed to classify schizophrenic and healthy patients based on their SNPs, DNA Methylation and fMRI data. Kernel and Multiple Kernel CCA are popular methods for finding nonlinear correlations between high-dimensional datasets. Data was gathered from 183 patients, 79 with schizophrenia and 104 healthy controls. Kernel and Multiple Kernel CCA represent new avenues for studying schizophrenia, because, to our knowledge, these methods have not been used on these data before. Classification is performed via k-means clustering on the kernel matrix outputs of the Kernel and Multiple Kernel CCA algorithm. Accuracies of the Kernel and Multiple Kernel CCA classification are compared to that of the regularized linear CCA algorithm classification, and are found to be significantly more accurate. Both algorithms demonstrate maximal accuracies when the combination of DNA methylation and fMRI data are used, and experience lower accuracies when the SNP data are incorporated.

Md ashad Alam, Osamu Komori, Yu-Ping Wang

In genome-wide interaction studies, to detect gene-gene interactions, most methods are divided into two folds: single nucleotide polymorphisms (SNP) based and gene-based methods. Basically, the methods based on the gene are more effective than the methods based on a single SNP. Recent years, while the kernel canonical correlation analysis (Classical kernel CCA) based U statistic (KCCU) has proposed to detect the nonlinear relationship between genes. To estimate the variance in KCCU, they have used resampling based methods which are highly computationally intensive. In addition, classical kernel CCA is not robust to contaminated data. We, therefore, first discuss robust kernel mean element, the robust kernel covariance, and cross-covariance operators. Second, we propose a method based on influence function to estimate the variance of the KCCU. Third, we propose a nonparametric robust KCCU method based on robust kernel CCA, which is designed for contaminated data and less sensitive to noise than classical kernel CCA. Finally, we investigate the proposed methods to synthesized data and imaging genetic data set. Based on gene ontology and pathway analysis, the synthesized and genetics analysis demonstrate that the proposed robust method shows the superior performance of the state-of-the-art methods.

Md Ashad Alam, Yu-Ping Wang

Imaging genetic research has essentially focused on discovering unique and co-association effects, but typically ignoring to identify outliers or atypical objects in genetic as well as non-genetics variables. Identifying significant outliers is an essential and challenging issue for imaging genetics and multiple sources data analysis. Therefore, we need to examine for transcription errors of identified outliers. First, we address the influence function (IF) of kernel mean element, kernel covariance operator, kernel cross-covariance operator, kernel canonical correlation analysis (kernel CCA) and multiple kernel CCA. Second, we propose an IF of multiple kernel CCA, which can be applied for more than two datasets. Third, we propose a visualization method to detect influential observations of multiple sources of data based on the IF of kernel CCA and multiple kernel CCA. Finally, the proposed methods are capable of analyzing outliers of subjects usually found in biomedical applications, in which the number of dimension is large. To examine the outliers, we use the stem-and-leaf display. Experiments on both synthesized and imaging genetics data (e.g., SNP, fMRI, and DNA methylation) demonstrate that the proposed visualization can be applied effectively.

Md. Ashad Alam, Kenji Fukumizu, Yu-Ping Wang

To the best of our knowledge, there are no general well-founded robust methods for statistical unsupervised learning. Most of the unsupervised methods explicitly or implicitly depend on the kernel covariance operator (kernel CO) or kernel cross-covariance operator (kernel CCO). They are sensitive to contaminated data, even when using bounded positive definite kernels. First, we propose robust kernel covariance operator (robust kernel CO) and robust kernel crosscovariance operator (robust kernel CCO) based on a generalized loss function instead of the quadratic loss function. Second, we propose influence function of classical kernel canonical correlation analysis (classical kernel CCA). Third, using this influence function, we propose a visualization method to detect influential observations from two sets of data. Finally, we propose a method based on robust kernel CO and robust kernel CCO, called robust kernel CCA, which is designed for contaminated data and less sensitive to noise than classical kernel CCA. The principles we describe also apply to many kernel methods which must deal with the issue of kernel CO or kernel CCO. Experiments on synthesized and imaging genetics analysis demonstrate that the proposed visualization and robust kernel CCA can be applied effectively to both ideal data and contaminated data. The robust methods show the superior performance over the state-of-the-art methods.