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.

With digitisation and the development of computer-aided diagnosis, histopathological image analysis has attracted considerable interest in recent years. In this article, we address the problem of the automated annotation of skin biopsy images, a special type of histopathological image analysis. In contrast to previous well-studied methods in histopathology, we propose a novel annotation method based on a multi-instance learning framework. The proposed framework first represents each skin biopsy image as a multi-instance sample using a graph cutting method, decomposing the image to a set of visually disjoint regions. Then, we construct two classification models using multi-instance learning algorithms, among which one provides determinate results and the other calculates a posterior probability. We evaluate the proposed annotation framework using a real dataset containing 6691 skin biopsy images, with 15 properties as target annotation terms. The results indicate that the proposed method is effective and medically acceptable.

Chronic neck pain is a common morbid disorder in modern society. Acupuncture has been administered for treating chronic pain as an alternative therapy for a long time, with its effectiveness supported by the latest clinical evidence. However, the potential effective difference in different syndrome types is questioned due to the limits of sample size and statistical methods. We applied machine learning methods in an attempt to solve this problem. Through a multi-objective sorting of subjective measurements, outstanding samples are selected to form the base of our kernel-oriented model. With calculation of similarities between the concerned sample and base samples, we are able to make full use of information contained in the known samples, which is especially effective in the case of a small sample set. To tackle the parameters selection problem in similarity learning, we propose an ensemble version of slightly different parameter setting to obtain stronger learning. The experimental result on a real data set shows that compared to some previous well-known methods, the proposed algorithm is capable of discovering the underlying difference among different syndrome types and is feasible for predicting the effective tendency in clinical trials of large samples.

Objective. This study aims to establish a model to analyze clinical experience of TCM veteran doctors. We propose an ensemble learning based framework to analyze clinical records with ICD‐10 labels information for effective diagnosis and acupoints recommendation. Methods. We propose an ensemble learning framework for the analysis task. A set of base learners composed of decision tree (DT) and support vector machine (SVM) are trained by bootstrapping the training dataset. The base learners are sorted by accuracy and diversity through nondominated sort (NDS) algorithm and combined through a deep ensemble learning strategy. Results. We evaluate the proposed method with comparison to two currently successful methods on a clinical diagnosis dataset with manually labeled ICD‐10 information. ICD‐10 label annotation and acupoints recommendation are evaluated for three methods. The proposed method achieves an accuracy rate of 88.2% ± 2.8% measured by zero‐one loss for the first evaluation session and 79.6% ± 3.6% measured by Hamming loss, which are superior to the other two methods. Conclusion. The proposed ensemble model can effectively model the implied knowledge and experience in historic clinical data records. The computational cost of training a set of base learners is relatively low.

Applying machine learning technology to automatic image analysis and auxiliary diagnosis of whole slide image (WSI) may help to improve the efficiency, objectivity, and consistency of pathological diagnosis. Due to its extremely high resolution, it is still a great challenge to directly process WSI through deep neural networks. In this paper, we propose a novel model for the task of classification of WSIs. The model is composed of two parts. The first part is a self‐supervised encoding network with a UNet‐like architecture. Each patch from a WSI is encoded as a compressed latent representation. These features are placed according to their corresponding patch’s original location in WSI, forming a feature cube. The second part is a classification network fused by 4 famous network blocks with heterogeneous architectures, with feature cube as input. Our model effectively expresses the feature and preserves location information of each patch. The fused network integrates heterogeneous features generated by different networks which yields robust classification results. The model is evaluated on two public datasets with comparison to baseline models. The evaluation results show the effectiveness of the proposed model.

Automatic classification of histopathological images plays an important role in computer-aided diagnosis systems. The automatic classification model of histopathological images based on deep neural networks has received widespread attention. However, the performance of deep models is affected by many factors, such as training hyperparameters, model structure, dataset quality, and training cost. In order to reduce the impact of the above factors on model training and reduce the training and inference costs of the model, we propose a novel method based on model fusion in the weight space, which is inspired by stochastic weight averaging and model soup. We use the cyclical learning rate (CLR) strategy to fine-tune the ingredient models and propose a ranking strategy based on accuracy and diversity for candidate model selection. Compared to the single model, the weight fusion of ingredient models can obtain a model whose performance is closer to the expected value of the error basin, which may improve the generalization ability of the model. Compared to the ensemble model with n base models, the testing cost of the proposed model is theoretically $1/n$ of that of the ensemble model. Experimental results on two histopathological image datasets show the effectiveness of the proposed model in comparison to baseline ones, including ResNet, VGG, DenseNet, and their ensemble versions.