Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

Pattern Recognition and Machine Learning

Malaria is a blood disease caused by the Plasmodium parasites transmitted through the bite of female Anopheles mosquito. Microscopists commonly examine thick and thin blood smears to diagnose disease and compute parasitemia. However, their accuracy depends on smear quality and expertise in classifying and counting parasitized and uninfected cells. Such an examination could be arduous for large-scale diagnoses resulting in poor quality. State-of-the-art image-analysis based computer-aided diagnosis (CADx) methods using machine learning (ML) techniques, applied to microscopic images of the smears using hand-engineered features demand expertise in analyzing morphological, textural, and positional variations of the region of interest (ROI). In contrast, Convolutional Neural Networks (CNN), a class of deep learning (DL) models promise highly scalable and superior results with end-to-end feature extraction and classification. Automated malaria screening using DL techniques could, therefore, serve as an effective diagnostic aid. In this study, we evaluate the performance of pre-trained CNN based DL models as feature extractors toward classifying parasitized and uninfected cells to aid in improved disease screening. We experimentally determine the optimal model layers for feature extraction from the underlying data. Statistical validation of the results demonstrates the use of pre-trained CNNs as a promising tool for feature extraction for this purpose.

Pre-trained convolutional neural networks as feature extractors toward improved malaria parasite detection in thin blood smear images

Image analysis and machine learning for detecting malaria

Deep learning in clinical natural language processing: a methodical review.

Malaria is a major global health threat. The standard way of diagnosing malaria is by visually examining blood smears for parasite-infected red blood cells under the microscope by qualified technicians. This method is inefficient and the diagnosis depends on the experience and the knowledge of the person doing the examination. Automatic image recognition technologies based on machine learning have been applied to malaria blood smears for diagnosis before. However, the practical performance has not been sufficient so far. This study proposes a new and robust machine learning model based on a convolutional neural network (CNN) to automatically classify single cells in thin blood smears on standard microscope slides as either infected or uninfected. In a ten-fold cross-validation based on 27,578 single cell images, the average accuracy of our new 16-layer CNN model is 97.37%. A transfer learning model only achieves 91.99% on the same images. The CNN model shows superiority over the transfer learning model in all performance indicators such as sensitivity (96.99% vs 89.00%), specificity (97.75% vs 94.98%), precision (97.73% vs 95.12%), F1 score (97.36% vs 90.24%), and Matthews correlation coefficient (94.75% vs 85.25%).

CNN-based image analysis for malaria diagnosis

Genomic variations are associated with the metabolism and the occurrence of adverse reactions of many therapeutic agents. The polymorphisms on over 2000 locations of cytochrome P450 enzymes (CYP) due to many factors such as ethnicity, mutations, and inheritance attribute to the diversity of response and side effects of various drugs. The associations of the single nucleotide polymorphisms (SNPs), the internal pharmacokinetic patterns and the vulnerability of specific adverse reactions become one of the research interests of pharmacogenomics. The conventional genomewide association studies (GWAS) mainly focuses on the relation of single or multiple SNPs to a specific risk factors which are a one-to-many relation. However, there are no robust methods to establish a many-to-many network which can combine the direct and indirect associations between multiple SNPs and a serial of events (e.g. adverse reactions, metabolic patterns, prognostic factors etc.). In this paper, we present a novel deep learning model based on generative stochastic networks and hidden Markov chain to classify the observed samples with SNPs on five loci of two genes (CYP2D6 and CYP1A2) respectively to the vulnerable population of 14 types of adverse reactions. A supervised deep learning model is proposed in this study. The revised generative stochastic networks (GSN) model with transited by the hidden Markov chain is used. The data of the training set are collected from clinical observation. The training set is composed of 83 observations of blood samples with the genotypes respectively on CYP2D6*2, *10, *14 and CYP1A2*1C, *1 F. The samples are genotyped by the polymerase chain reaction (PCR) method. A hidden Markov chain is used as the transition operator to simulate the probabilistic distribution. The model can perform learning at lower cost compared to the conventional maximal likelihood method because the transition distribution is conditional on the previous state of the hidden Markov chain. A least square loss (LASSO) algorithm and a k-Nearest Neighbors (kNN) algorithm are used as the baselines for comparison and to evaluate the performance of our proposed deep learning model. There are 53 adverse reactions reported during the observation. They are assigned to 14 categories. In the comparison of classification accuracy, the deep learning model shows superiority over the LASSO and kNN model with a rate over 80 %. In the comparison of reliability, the deep learning model shows the best stability among the three models. Machine learning provides a new method to explore the complex associations among genomic variations and multiple events in pharmacogenomics studies. The new deep learning algorithm is capable of classifying various SNPs to the corresponding adverse reactions. We expect that as more genomic variations are added as features and more observations are made, the deep learning model can improve its performance and can act as a black-box but reliable verifier for other GWAS studies.

/pdf/dl-adr-a-novel-deep-learning-model-for-classifying-genomic-165e8250p4.pdf

DL-ADR: a novel deep learning model for classifying genomic variants into adverse drug reactions

Deep generative learning for automated EHR diagnosis of traditional Chinese medicine.

The severe pneumonia induced by the infection of the SARS-CoV-2 virus causes massive death in the ongoing COVID-19 pandemic. The early detection of the SARS-CoV-2 induced pneumonia relies on the unique patterns of the chest XRay images. Deep learning is a data-greedy algorithm to achieve high performance when adequately trained. A common challenge for machine learning in the medical domain is the accessibility to properly annotated data. In this study, we apply a conditional adversarial network (cGAN) to perform image to image (Pix2Pix) translation from the non-COVID-19 chest X-Ray domain to the COVID-19 chest X-Ray domain. The objective is to learn a mapping from the normal chest X-Ray visual patterns to the COVID-19 pneumonia chest X-ray patterns. The original dataset has a typical imbalanced issue because it contains only 219 COVID-19 positive images but has 1,341 images for normal chest X-Ray and 1,345 images for viral pneumonia. A U-Net based architecture is applied for the image-to-image translation to generate synthesized COVID-19 X-Ray chest images from the normal chest X-ray images. A 50-convolutional-layer residual net (ResNet) architecture is applied for the final classification task. After training the GAN model for 100 epochs, we use the GAN generator to translate 1,100 COVID-19 images from the normal X-Ray to form a balanced training dataset (3,762 images) for the classification task. The ResNet based classifier trained by the enhanced dataset achieves the classification accuracy of 97.8% compared to 96.1% in the transfer learning mode. When trained with the original imbalanced dataset, the model achieves an accuracy of 96.1% compared to 95.6% in the training from trainby-scratch model. In addition, the classifier trained by the enhanced dataset has more stable measures in precision, recall, and F1 scores across different image classes. We conclude that the GAN-based data enhancement strategy is applicable to most medical image pattern recognition tasks, and it provides an effective way to solve the common expertise dependence issue in the medical domain.

/pdf/enhancing-automated-covid-19-chest-x-ray-diagnosis-by-image-32clm03evy.pdf

Enhancing Automated COVID-19 Chest X-ray Diagnosis by Image-to-Image GAN Translation

The genetic polymorphism of Cytochrome P450 (CYP 450) is considered as one of the main causes for adverse drug reactions (ADRs). In order to explore the latent correlations between ADRs and the genetic polymorphism, a new model is proposed in which both the inputs of the genetic locuses (i.e.CYP2D6*2, CYP2D6*10, CYP2D6*14, CYP1A2*1C and CYP1A2*1F) and occurrence as probabilistic distribution. A generative model is proposed to describe the joint distributions of occurrence of ADRs and the diversity of genetic sub-types of the input variables. The new algorithm is developed based on Generative Stochastic Networks (GSN) model. A Markov chain from a training data set is applied for the learning as a transition operator to simulate a probabilistic distribution. The transition distribution is conditional on the previous step of the chain thus it is able to perform learning at a much lower cost than the conventional maximal likelihood method. The experiment results show that the newly algorithm is more effective than the available conventional methods.

Zhaohui Liang

Papers

CNN-based image analysis for malaria diagnosis

DL-ADR: a novel deep learning model for classifying genomic variants into adverse drug reactions

Deep generative learning for automated EHR diagnosis of traditional Chinese medicine.

Enhancing Automated COVID-19 Chest X-ray Diagnosis by Image-to-Image GAN Translation

Discovery of the relations between genetic polymorphism and adverse drug reactions