Project description:The analytes qualified as biomarkers are potent tools to diagnose various diseases, monitor therapy responses, and design therapeutic interventions. The early assessment of the diverseness of human disease is essential for the speedy and cost-efficient implementation of personalized medicine. We developed g3mclass, the Gaussian mixture modeling software for molecular assay data classification. This software automates the validated multiclass classifier applicable to single analyte tests and multiplexing assays. The g3mclass achieves automation using the original semi-constrained expectation-maximization (EM) algorithm that allows inference from the test, control, and query data that human experts cannot interpret. In this study, we used real-world clinical data and gene expression datasets (ERBB2, ESR1, PGR) to provide examples of how g3mclass may help overcome the problems of over-/underdiagnosis and equivocal results in diagnostic tests for breast cancer. We showed the g3mclass output’s accuracy, robustness, scalability, and interpretability. The user-friendly interface and free dissemination of this multi-platform software aim to ease its use by research laboratories, biomedical pharma, companion diagnostic developers, and healthcare regulators. Furthermore, the g3mclass automatic extracting information through probabilistic modeling is adaptable for blending with machine learning and artificial intelligence.
Project description:The analytes qualified as biomarkers are potent tools to diagnose various diseases, monitor therapy responses, and design therapeutic interventions. The early assessment of the diverseness of human disease is essential for the speedy and cost-efficient implementation of personalized medicine. We developed g3mclass, the Gaussian mixture modeling software for molecular assay data classification. This software automates the validated multiclass classifier applicable to single analyte tests and multiplexing assays. The g3mclass achieves automation using the original semi-constrained expectation-maximization (EM) algorithm that allows inference from the test, control, and query data that human experts cannot interpret. In this study, we used real-world clinical data and gene expression datasets (ERBB2, ESR1, PGR) to provide examples of how g3mclass may help overcome the problems of over-/underdiagnosis and equivocal results in diagnostic tests for breast cancer. We showed the g3mclass output's accuracy, robustness, scalability, and interpretability. The user-friendly interface and free dissemination of this multi-platform software aim to ease its use by research laboratories, biomedical pharma, companion diagnostic developers, and healthcare regulators. Furthermore, the g3mclass automatic extracting information through probabilistic modeling is adaptable for blending with machine learning and artificial intelligence.
Project description:Diffuse Large B Cell Lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Despite being considered a single disease, DLBCL presents with variable backgrounds in terms of morphology, genetics, and biological behavior, which results in heterogeneous outcomes among patients. Although new tools have been developed for the classification and management of patients, 40% of them still have primary refractory disease or relapse. In addition, multiple factors regarding the pathogenesis of this disease remain unclear and identification of novel biomarkers is needed. In this context, recent investigations point to microRNAs as useful biomarkers in cancer as well as important players in the development of the disease. However, regarding DLBCL, up to date, there is inconsistency in the data reported. Therefore, in this work, the main goals were to determine a microRNA set with utility as biomarkers for DLBCL diagnosis, classification, prognosis and treatment response. To achieve these goals, we analyzed microRNA expression in a cohort of 78 DLBCL samples at diagnosis and 17 controls using small RNA sequencing. This way, we were able to define new microRNA expression signatures for diagnosis, classification, treatment response and prognosis. In summary, our study remarks that microRNAs could play an important role as biomarkers in diagnosis, classification, treatment response and prognosis in DLBCL.
Project description:There are many toxic chemicals to contaminate the world and cause harm to human and other organisms. How to quickly discriminate these compounds and characterize their potential molecular mechanism and toxicity is essential. High through put transcriptomics profiles such as microarray have been proven useful to identify biomarkers for different classification and toxicity prediction purposes. Here we aim to investigate how to use microarray to predict chemical contaminants and their possible mechanisms. In this study, we divided 105 compounds plus vehicle control into 14 compound classes. On the basis of gene expression profiles of in vitro primary cultured hepatocytes, we comprehensively compared various normalization, feature selection and classification algorithms for the classification of these 14 class compounds. We found that normalization had little effect on the averaged classification accuracy. Two support vector machine methods LibSVM and SMO had better classification performance. When feature sizes were smaller, LibSVM outperformed other classification methods. Simple logistic algorithm also performed well. At the training stage, usually the feature selection method SVM-RFE performed the best, and PCA was the poorest feature selection algorithm. But overall, SVM-RFE had the highest overfitting rate when an independent dataset used for a prediction in this case. Therefore, we developed a new feature selection algorithm called gradient method which had a pretty high training classification as well as prediction accuracy with the lowest over-fitting rate. Through the analysis of biomarkers that distinguished 14 class compounds, we found a goup of genes that mainly invovled in cell cylce were significanly downregulated by the metal and inflammatory compounds, but were induced by anti-microbial, cancer related drugs, pesticides, and PXR mediators. For in vitro experiment, primary cultured rat hepatocytes were treated one of 105 compounds with relative controls. At least three biological replicates were used for each unique condition. In total 531 arrays were used.
Project description:There are many toxic chemicals to contaminate the world and cause harm to human and other organisms. How to quickly discriminate these compounds and characterize their potential molecular mechanism and toxicity is essential. High through put transcriptomics profiles such as microarray have been proven useful to identify biomarkers for different classification and toxicity prediction purposes. Here we aim to investigate how to use microarray to predict chemical contaminants and their possible mechanisms. In this study, we divided 105 compounds plus vehicle control into 14 compound classes. On the basis of gene expression profiles of in vitro primary cultured hepatocytes, we comprehensively compared various normalization, feature selection and classification algorithms for the classification of these 14 class compounds. We found that normalization had little effect on the averaged classification accuracy. Two support vector machine methods LibSVM and SMO had better classification performance. When feature sizes were smaller, LibSVM outperformed other classification methods. Simple logistic algorithm also performed well. At the training stage, usually the feature selection method SVM-RFE performed the best, and PCA was the poorest feature selection algorithm. But overall, SVM-RFE had the highest overfitting rate when an independent dataset used for a prediction in this case. Therefore, we developed a new feature selection algorithm called gradient method which had a pretty high training classification as well as prediction accuracy with the lowest over-fitting rate. Through the analysis of biomarkers that distinguished 14 class compounds, we found a goup of genes that mainly invovled in cell cylce were significanly downregulated by the metal and inflammatory compounds, but were induced by anti-microbial, cancer related drugs, pesticides, and PXR mediators.
Project description:To identify the potential biomarkers of Alzheimer's disease (AD) based on circulating microRNAs (miRNAs), we developed a new approach using feature selection and linear mixed model. The miRNA sequencing data of 105 plasma and 112 serum samples from 112 subjects including 28 AD cases, 63 mild cognitive impairment (MCI), and 21 controls were used to identify cerebrospinal fluid biomarkers associated miRNAs. The potential of these miRNAs as biomarkers of AD or MCI was researched and validated via both internal and external dataset. Patient classification was effectuated in compliance with the NIA-AA criteria for “MCI due to AD” and “Dementia due to AD”.