Dataset Information

A Toolbox for Functional Analysis and the Systematic Identification of Diagnostic and Prognostic Gene Expression Signatures Combining Meta-Analysis and Machine Learning.

ABSTRACT: The identification of biomarker signatures is important for cancer diagnosis and prognosis. However, the detection of clinical reliable signatures is influenced by limited data availability, which may restrict statistical power. Moreover, methods for integration of large sample cohorts and signature identification are limited. We present a step-by-step computational protocol for functional gene expression analysis and the identification of diagnostic and prognostic signatures by combining meta-analysis with machine learning and survival analysis. The novelty of the toolbox lies in its all-in-one functionality, generic design, and modularity. It is exemplified for lung cancer, including a comprehensive evaluation using different validation strategies. However, the protocol is not restricted to specific disease types and can therefore be used by a broad community. The accompanying R package vignette runs in ~1 h and describes the workflow in detail for use by researchers with limited bioinformatics training.

SUBMITTER: Vey J

PROVIDER: S-EPMC6827106 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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A Toolbox for Functional Analysis and the Systematic Identification of Diagnostic and Prognostic Gene Expression Signatures Combining Meta-Analysis and Machine Learning.

Vey Johannes J Kapsner Lorenz A. LA Fuchs Maximilian M Unberath Philipp P Veronesi Giulia G Kunz Meik M

Cancers 20191021 10

The identification of biomarker signatures is important for cancer diagnosis and prognosis. However, the detection of clinical reliable signatures is influenced by limited data availability, which may restrict statistical power. Moreover, methods for integration of large sample cohorts and signature identification are limited. We present a step-by-step computational protocol for functional gene expression analysis and the identification of diagnostic and prognostic signatures by combining meta-a ...[more]

PMID: 31640282

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Project description:BackgroundDiagnostic models based on gene signatures of nasopharyngeal carcinoma (NPC) were constructed by random forest (RF) and artificial neural network (ANN) algorithms. Least absolute shrinkage and selection operator (Lasso)-Cox regression was used to select and build prognostic models based on gene signatures. This study contributes to the early diagnosis and treatment, prognosis, and molecular mechanisms associated with NPC.MethodsTwo gene expression datasets were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) associated with NPC were identified by gene expression differential analysis. Subsequently, significant DEGs were identified by a RF algorithm. ANN were used to construct a diagnostic model for NPC. The performance of the diagnostic model was evaluated by area under the curve (AUC) values using a validation set. Lasso-Cox regression examined gene signatures associated with prognosis. Overall survival (OS) and disease-free survival (DFS) prediction models were constructed and validated from The Cancer Genome Atlas (TCGA) database and the International Cancer Genome Consortium (ICGC) database.ResultsA total of 582 DEGs associated with NPC were identified, and 14 significant genes were identified by the RF algorithm. A diagnostic model for NPC was successfully constructed using ANN, and the validity of the model was confirmed on the training set AUC =0.947 [95% confidence interval (CI): 0.911-0.969] and the validation set AUC =0.864 (95% CI: 0.828-0.901). The 24-gene signatures associated with prognosis were identified by Lasso-Cox regression, and prediction models for OS and DFS of NPC were constructed on the training set. Finally, the ability of the model was validated on the validation set.ConclusionsSeveral potential gene signatures associated with NPC were identified, and a high-performance predictive model for early diagnosis of NPC and a prognostic prediction model with robust performance were successfully developed. The results of this study provide valuable references for early diagnosis, screening, treatment and molecular mechanism research of NPC in the future.

Project description:PurposeA significant hurdle in developing reliable gene expression-based prognostic models has been the limited sample size, which can cause overfitting and false discovery. Combining data from multiple studies can enhance statistical power and reduce spurious findings, but how to address the biologic heterogeneity across different datasets remains a major challenge. Better meta-survival analysis approaches are needed.Material and methodsWe presented a decentralized learning framework for meta-survival analysis without the need for data aggregation. Our method consisted of a series of proposals that together alleviated the influence of data heterogeneity and improved the performance of survival prediction. First, we transformed the gene expression profile of every sample into normalized percentile ranks to obtain platform-agnostic features. Second, we used Stouffer's meta-z approach in combination with Harrell's concordance index to prioritize and select genes to be included in the model. Third, we used survival discordance as a scale-independent model loss function. Instead of generating a merged dataset and training the model therein, we avoided comparing patients across datasets and individually evaluated the loss function on each dataset. Finally, we optimized the model by minimizing the joint loss function.ResultsThrough comprehensive evaluation on 31 public microarray datasets containing 6,724 samples of several cancer types, we demonstrated that the proposed method has outperformed (1) single prognostic genes identified using conventional meta-analysis, (2) multigene signatures trained on single datasets, (3) multigene signatures trained on merged datasets as well as by other existing meta-analysis methods, and (4) clinically applicable, established multigene signatures.ConclusionThe decentralized learning approach can be used to effectively perform meta-analysis of gene expression data and to develop robust multigene prognostic signatures.

Project description:The human microbiome has become an area of intense research due to its potential impact on human health. However, the analysis and interpretation of this data have proven to be challenging due to its complexity and high dimensionality. Machine learning (ML) algorithms can process vast amounts of data to uncover informative patterns and relationships within the data, even with limited prior knowledge. Therefore, there has been a rapid growth in the development of software specifically designed for the analysis and interpretation of microbiome data using ML techniques. These software incorporate a wide range of ML algorithms for clustering, classification, regression, or feature selection, to identify microbial patterns and relationships within the data and generate predictive models. This rapid development with a constant need for new developments and integration of new features require efforts into compile, catalog and classify these tools to create infrastructures and services with easy, transparent, and trustable standards. Here we review the state-of-the-art for ML tools applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on ML based software and framework resources currently available for the analysis of microbiome data in humans. The aim is to support microbiologists and biomedical scientists to go deeper into specialized resources that integrate ML techniques and facilitate future benchmarking to create standards for the analysis of microbiome data. The software resources are organized based on the type of analysis they were developed for and the ML techniques they implement. A description of each software with examples of usage is provided including comments about pitfalls and lacks in the usage of software based on ML methods in relation to microbiome data that need to be considered by developers and users. This review represents an extensive compilation to date, offering valuable insights and guidance for researchers interested in leveraging ML approaches for microbiome analysis.

Project description:BackgroundDental plaque microbes play a key role in the development of periodontal disease. Numerous high-throughput sequencing studies have generated understanding of the bacterial species associated with both canine periodontal health and disease. Opportunities therefore exist to utilise these bacterial biomarkers to improve disease diagnosis in conscious-based veterinary oral health checks. Here, we demonstrate that molecular techniques, specifically quantitative polymerase chain reaction (qPCR) can be utilised for the detection of microbial biomarkers associated with canine periodontal health and disease.ResultsOver 40 qPCR assays targeting single microbial species associated with canine periodontal health, gingivitis and early periodontitis were developed and validated. These were used to quantify levels of the respective taxa in canine subgingival plaque samples collected across periodontal health (PD0), gingivitis (PD1) and early periodontitis (PD2). When qPCR outputs were compared to the corresponding high-throughput sequencing data there were strong correlations, including a periodontal health associated taxa, Capnocytophaga sp. COT-339 (rs =0.805), and two periodontal disease associated taxa, Peptostreptococcaceae XI [G-4] sp. COT-019 (rs=0.902) and Clostridiales sp. COT-028 (rs=0.802). The best performing models, from five machine learning approaches applied to the qPCR data for these taxa, estimated 85.7% sensitivity and 27.5% specificity for Capnocytophaga sp. COT-339, 74.3% sensitivity and 67.5% specificity for Peptostreptococcaceae XI [G-4] sp. COT-019, and 60.0% sensitivity and 80.0% specificity for Clostridiales sp. COT-028.ConclusionsA qPCR-based approach is an accurate, sensitive, and cost-effective method for detection of microbial biomarkers associated with periodontal health and disease. Taken together, the correlation between qPCR and high-throughput sequencing outputs, and early accuracy insights, indicate the strategy offers a prospective route to the development of diagnostic tools for canine periodontal disease.

Project description:Data from omics studies have been used for prediction and classification of various diseases in biomedical and bioinformatics research. In recent years, Machine Learning (ML) algorithms have been used in many different fields related to healthcare systems, especially for disease prediction and classification tasks. Integration of molecular omics data with ML algorithms has offered a great opportunity to evaluate clinical data. RNA sequence (RNA-seq) analysis has been emerged as the gold standard for transcriptomics analysis. Currently, it is being used widely in clinical research. In our present work, RNA-seq data of extracellular vesicles (EV) from healthy and colon cancer patients are analyzed. Our aim is to develop models for prediction and classification of colon cancer stages. Five different canonical ML and Deep Learning (DL) classifiers are used to predict colon cancer of an individual with processed RNA-seq data. The classes of data are formed on the basis of both colon cancer stages and cancer presence (healthy or cancer). The canonical ML classifiers, which are k-Nearest Neighbor (kNN), Logistic Model Tree (LMT), Random Tree (RT), Random Committee (RC), and Random Forest (RF), are tested with both forms of the data. In addition, to compare the performance with canonical ML models, One-Dimensional Convolutional Neural Network (1-D CNN), Long Short-Term Memory (LSTM), and Bidirectional LSTM (BiLSTM) DL models are utilized. Hyper-parameter optimizations of DL models are constructed by using genetic meta-heuristic optimization algorithm (GA). The best accuracy in cancer prediction is obtained with RC, LMT, and RF canonical ML algorithms as 97.33%. However, RT and kNN show 95.33% performance. The best accuracy in cancer stage classification is achieved with RF as 97.33%. This result is followed by LMT, RC, kNN, and RT with 96.33%, 96%, 94.66%, and 94%, respectively. According to the results of the experiments with DL algorithms, the best accuracy in cancer prediction is obtained with 1-D CNN as 97.67%. BiLSTM and LSTM show 94.33% and 93.67% performance, respectively. In classification of the cancer stages, the best accuracy is achieved with BiLSTM as 98%. 1-D CNN and LSTM show 97% and 94.33% performance, respectively. The results reveal that both canonical ML and DL models may outperform each other for different numbers of features.

Dataset Information

A Toolbox for Functional Analysis and the Systematic Identification of Diagnostic and Prognostic Gene Expression Signatures Combining Meta-Analysis and Machine Learning.

Publications

A Toolbox for Functional Analysis and the Systematic Identification of Diagnostic and Prognostic Gene Expression Signatures Combining Meta-Analysis and Machine Learning.

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