Implementing and Evaluating a Gaussian Mixture Framework for Identifying Gene Function from TnSeq Data

The rapid acceleration of microbial genome sequencing increases opportunities to understand bacterial gene function. Unfortunately, only a small proportion of genes have been studied. Recently, TnSeq has been proposed as a cost-effective, highly reliable approach to predict gene functions as a response to changes in a cell\u27s fitness before-after genomic changes. However, major questions remain about how to best determine whether an observed quantitative change in fitness represents a meaningful change. To address the limitation, we develop a Gaussian mixture model framework for classifying gene function from TnSeq experiments. In order to implement the mixture model, we present the Expectation-Maximization algorithm and a hierarchical Bayesian model sampled using Stan\u27s Hamiltonian Monte-Carlo sampler. We compare these implementations against the frequentist method used in current TnSeq literature. From simulations and real data produced by E.coli TnSeq experiments, we show that the Bayesian implementation of the Gaussian mixture framework provides the most consistent classification results

Insights from Systematically Analyzing Microbial Phenotypic Profiles

Following classical genetic approaches to understanding gene function, high-throughput phenotyping methods have emerged as a new way of studying gene functions, especially in microorganisms, which are highly amenable to high-throughput experimental design. As more high-throughput microbial phenotype data as well as the low-throughput data become available, systematically managing, displaying, and analyzing these data become a pivotal part in discovering unknown functions for genes. In this work, I have curated some datasets for high-throughput microbial phenotype data that contain genomic-scale phenotypes from E. coli tested under hundreds of conditions. Next, I conducted systematic and unbiased statistical analysis of these phenotype datasets and showed that the phenotypic profiles within these datasets are highly correlated with various functional annotations. The phenotype-function correlation has also been seen when a curated cell-cycle related phenotypic profile of S. cerevisiae is used with Gene Ontology annotations. Furthermore, I have displayed the preliminary results of using machine learning techniques to predict gene functions using high-throughput phenotype data of complete annotations, given more functional annotations as labels. Lastly, I describe a software package written in R that is potentially useful in analyzing high-throughput microbial phenotype data

Biocomputing 2019 - Proceedings Of The Pacific Symposium

Intro -- Preface -- PATTERN RECOGNITION IN BIOMEDICAL DATA: CHALLENGES IN PUTTING BIG DATA TO WORK -- Session introduction -- Introduction -- References -- Learning Contextual Hierarchical Structure of Medical Concepts with Poincairé Embeddings to Clarify Phenotypes -- 1. Introduction -- 2. Methods -- 2.1. Source Code -- 2.2. Data Source -- 2.3. Data Selection and Preprocessing -- 2.3.1. Reference ICD9 Example -- 2.3.2. Real Member Analyses -- 2.4. Poincaré Embeddings -- 2.5. Processing and Evaluating Embeddings -- 3. Results -- 3.1. ICD9 Hierarchy Evaluation -- 3.2. Poincaré Embeddings on 10 Million Members -- 3.3. Comparison with Euclidean Embeddings -- 3.4. Cohort Specific Embeddings -- 4. Discussion and Conclusion -- 5. Acknowledgments -- References -- The Effectiveness of Multitask Learning for Phenotyping with Electronic Health Records Data -- 1. Introduction -- 2. Background -- 2.1. Multitask nets -- 3. Methods -- 3.1. Dataset Construction and Design -- 3.2. Experimental Design -- 4. Experiments and Results -- 4.1. When Does Multitask Learning Improve Performance? -- 4.2. Relationship Between Performance and Number of Tasks -- 4.3. Comparison with Logistic Regression Baseline -- 4.4. Interaction between Phenotype Prevalence and Complexity -- 5. Limitations -- 6. Conclusion -- Acknowledgments -- References -- ODAL: A one-shot distributed algorithm to perform logistic regressions on electronic health records data from multiple clinical sites -- 1. Introduction -- 1.1. Integrate evidence from multiple clinical sites -- 1.2. Distributed Computing -- 2. Material and Method -- 2.1. Clinical Cohort and Motivating Problem -- 2.2. Algorithm -- 2.3. Simulation Design -- 3. Results -- 3.1. Simulation Results -- 3.2. Fetal Loss Prediction via ODAL -- 4. Discussion -- ReferencesPVC Detection Using a Convolutional Autoencoder and Random Forest Classifier -- 1. Introduction -- 2. Methods -- 2.1. Data Set and Implementation -- 2.2. Proposed PVC Detection Method -- 2.2.1. Feature Extraction -- 2.2.2. Classification -- 3. Results -- 3.1. Full Database Evaluation -- 3.2. Timing Disturbance Evaluation -- 3.3. Cross-Patient Training Evaluation -- 3.4. Estimated Parameters and Convergence -- 4. Discussion -- References -- Removing Confounding Factors Associated Weights in Deep Neural Networks Improves the Prediction Accuracy for Healthcare Applications -- 1. Introduction -- 2. Related Work -- 3. Confounder Filtering (CF) Method -- 3.1. Overview -- 3.2. Method -- 3.3. Availability -- 4. Experiments -- 4.1. lung adenocarcinoma prediction -- 4.1.1. Data -- 4.1.2. Results -- 4.2. Segmentation on right ventricle(RV) of Heart -- 4.2.1. Data -- 4.2.2. Results -- 4.3. Students' confusion status prediction -- 4.3.1. Data -- 4.3.2. Results -- 4.4. Brain tumor prediction -- 4.4.1. Data -- 4.4.2. Results -- 4.5. Analyses of the method behaviors -- 5. Conclusion -- 6. Acknowledgement -- References -- DeepDom: Predicting protein domain boundary from sequence alone using stacked bidirectional LSTM -- 1. Introduction -- 2. METHODS -- 2.1 Data Set Preparation -- 2.2 Input Encoding -- 2.3 Model Architecture -- 2.4 Evaluation criteria -- 3. RESULTS AND DISCUSSION -- 3.1 Parameter configuration experiments on test data -- 3.2 Comparison with Other Domain Boundary Predictors -- 3.2.1 Free modeling targets from CASP 9 -- 3.2.2 Multi-domain targets from CASP 9 -- 3.2.3 Discontinuous domain target from CASP 8 -- 4. CONCLUSION -- 5. ACKNOWLEDGEMENTS -- REFERENCES -- Res2s2aM: Deep residual network-based model for identifying functional noncoding SNPs in trait-associated regions -- 1. Introduction -- 2. Background theory3. Dataset for training and testing -- 3.1. Source databases -- 3.2. Dataset generation -- 4. Methods -- 4.1. ResNet architecture in our model -- 4.2. Tandem inputs of forward- and reverse-strand sequences -- 4.3. Biallelic high-level network structure -- 4.4. Incorporating HaploReg SNP annotation features -- 4.5. Training of models -- 5. Results -- 6. Conclusions and discussion -- Acknowledgements -- References -- DNA Steganalysis Using Deep Recurrent Neural Networks -- 1. Introduction -- 2. Background -- 2.1. Notations -- 2.2. Hiding Messages -- 2.3. Determination of Message-Hiding Regions -- 3. Methods -- 3.1. Proposed DNA Steganalysis Principle -- 3.2. Proposed Steganalysis RNN Model -- 4. Results -- 4.1. Dataset -- 4.2. Input Representation -- 4.3. Model Training -- 4.4. Evaluation Procedure -- 4.5. Performance Comparison -- 5. Discussion -- Acknowledgments -- References -- Bi-directional Recurrent Neural Network Models for Geographic Location Extraction in Biomedical Literature -- 1. Introduction -- 2. Related Work -- 3. Methods -- 3.1. Toponym Detection -- 3.1.1. Recurrent Neural Networks -- 3.1.2. LSTM -- 3.1.3. Other Gated RNN Architectures -- 3.1.4. Hyperparameter search and optimization -- 3.2. Toponym Disambiguation -- 3.2.1. Building Geonames Index -- 3.2.2. Searching Geonames Index -- 4. Results and Discussion -- 4.1. Toponym Disambiguation -- 4.2. Toponym Resolution -- 5. Limitations and Future Work -- 6. Conclusion -- Acknowledgments -- Funding -- References -- Automatic Human-like Mining and Constructing Reliable Genetic Association Database with Deep Reinforcement Learning -- 1. Introduction -- 2. Related Work -- 3. Method -- 3.1. Model Framework -- 3.2. Deep Reinforcement Learning for Organizing Actions -- 3.3. Preprocessing and Name Entity Recognition with UMLS -- 3.4. Bidirectional LSTM for Relation Classification3.5. Algorithm -- 3.6. Implementation Specification -- 4. Experiments -- 4.1. Data -- 4.2. Evaluation -- 4.3. Results -- 4.3.1. Improved Reliability -- 4.3.2. Robustness in Real-world Situations -- 4.3.3. Number of Articles Read -- 5. Conclusions and Future Work -- 6. Acknowledgement -- References -- Estimating classification accuracy in positive-unlabeled learning: characterization and correction strategies -- 1. Introduction -- 2. Methods -- 2.1. Performance measures: definitions and estimation -- 2.2. Positive-unlabeled setting -- 2.3. Performance measure correction -- 3. Experiments and Results -- 3.1. A case study -- 3.2. Data sets -- 3.3. Experimental protocols -- 3.4. Results -- 4. Conclusions -- Acknowledgements -- References -- PLATYPUS: A Multiple-View Learning Predictive Framework for Cancer Drug Sensitivity Prediction -- 1. Introduction -- 2. System and methods -- 2.1. Data -- 2.2. Single views and co-training -- 2.3. Maximizing agreement across views through label assignment -- 3. Results -- 3.1. Preliminary experiments to optimize PLATYPUS performance -- 3.2. Predicting drug sensitivity in cell lines -- 3.3. Key features from PLATYPUS models -- 4. Conclusions -- Acknowledgments -- References -- Computational KIR copy number discovery reveals interaction between inhibitory receptor burden and survival -- 1. Introduction -- 2. Materials and Methods -- 2.1 Data collection -- 2.2 K-mer selection -- 2.3 NGS pipeline and k-mer extraction -- 2.4 Data cleaning -- 2.5 Normalization of k-mer frequencies -- 2.6 Copy number segregation and cutoff selection -- 2.7 Validation of copy number -- 2.8 Survival analysis -- 2.9 Additional immune analysis -- 3. Results and Discussions -- 3.1 Establishing unique k-mers -- 3.2 Varying coverage of KIR region by exome capture kit -- 3.3 Inference of KIR copy number -- 3.4 Population variation of the KIR region3.5 KIR inhibitory gene burden correlates with survival in cervical and uterine cancer -- 5. Conclusions -- 6. Acknowledgements -- 7. Supplementary Material -- References -- Exploring microRNA Regulation of Cancer with Context-Aware Deep Cancer Classifier -- 1. Introduction -- 2. Data -- 2.1. Preprocessing -- 3. Deep Cancer Classifier -- 3.1. Training &amp -- testing -- 3.2. Parameter tuning -- 3.3. Feature importance -- 4. Results and Discussion -- 4.1. Model selection -- 4.2. Classifier performance -- 4.3. Comparison with other methods -- 4.4. Feature importance -- 5. Conclusion -- References -- Implementing and Evaluating A Gaussian Mixture Framework for Identifying Gene Function from TnSeq Data -- 1. Introduction -- 1.1. TnSeq Motivation and Background -- 1.2. Motivation and New Methods -- 2. Methods -- 2.1. TnSeq Experimental Data -- 2.2. Mixture framework -- 2.3. Classification methods -- 2.3.1. Novel method - EM -- 2.3.2. Current method - t-statistic -- 2.3.3. Bayesian hierarchical model -- 2.3.4. Data partitioning for the Bayesian model -- 2.4. Simulation -- 2.5. Real data -- 3. Results -- 3.1.1. Classification rate -- 3.1.2. False positive rate -- 3.1.3. Positive classification rate -- 3.1.4. Cross entropy -- 3.2. Simulation Results -- 3.3. Comparisons on real data -- 3.4. Software -- 4. Discussion -- References -- SNPs2ChIP: Latent Factors of ChIP-seq to infer functions of non-coding SNPs -- 1. Introduction -- 2. Results -- 2.1. SNPs2ChIP analysis framework overview -- 2.2. Batch normalization of heterogeneous epigenetic features -- 2.3. Latent factor discovery and their biological characterization -- 2.4. SNPs2ChIP identifies relevant functions of the non-coding genome -- 2.4.1. Genome-wide SNPs coverage of the reference datasets -- 2.4.2. Non-coding GWAS SNPs of systemic lupus erythematosus -- 2.4.3. ChIP-seq peaks for vitamin D receptors2.5. Robustness Analysis in the latent factor identificationDescription based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries