The identification and quantification of markers in medical images is critical for diagnosis, prognosis, and disease management. Supervised machine learning enables the detection and exploitation of findings that are known a priori after annotation of training examples by experts. However, supervision does not scale well, due to the amount of necessary training examples, and the limitation of the marker vocabulary to known entities. In this proof-of-concept study, we propose unsupervised identification of anomalies as candidates for markers in retinal optical coherence tomography (OCT) imaging data without a constraint to a priori definitions. We identify and categorize marker candidates occurring frequently in the data and demonstrate that these markers show a predictive value in the task of detecting disease. A careful qualitative analysis of the identified data driven markers reveals how their quantifiable occurrence aligns with our current understanding of disease course, in early- and late age-related macular degeneration (AMD) patients. A multi-scale deep denoising autoencoder is trained on healthy images, and a one-class support vector machine identifies anomalies in new data. Clustering in the anomalies identifies stable categories. Using these markers to classify healthy-, early AMD- and late AMD cases yields an accuracy of 81.40 . In a second binary classification experiment on a publicly available data set (healthy versus intermediate AMD), the model achieves an area under the ROC curve of 0.944.
Examples for the classic biomarker identification strategy are @cite_18 @cite_29 , where the authors used a priori defined features in a supervised way to evaluate the applicability as biomarkers for specific diseases. In contrary, our approach focuses on identifying new marker candidates in an unsupervised way.
@cite_18 @cite_29
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Biomarker identification, i.e., detecting the features that indicate differences between two or more classes, is an important task in omics sciences. Mass spectrometry (MS) provide a high throughput analysis of proteomic and metabolomic data. The number of features of the MS data sets far exceeds the number of samples, making biomarker identification extremely difficult. Feature construction can provide a means for solving this problem by transforming the original features to a smaller number of high-level features. This paper investigates the construction of multiple features using genetic programming (GP) for biomarker identification and classification of mass spectrometry data. In this paper, multiple features are constructed using GP by adopting an embedded approach in which Fisher criterion and p-values are used to measure the discriminating information between the classes. This produces nonlinear high-level features from the low-level features for both binary and multi-class mass spectrometry data sets. Meanwhile, seven different classifiers are used to test the effectiveness of the constructed features. The proposed GP method is tested on eight different mass spectrometry data sets. The results show that the high-level features constructed by the GP method are effective in improving the classification performance in most cases over the original set of features and the low-level selected features. In addition, the new method shows superior performance in terms of biomarker detection rate. There are two major challenges to overcome when developing a classifier to perform automatic disease diagnosis. First, the amount of labeled medical data is typically very limited, and a classifier cannot be effectively trained to attain high disease-detection accuracy. Second, medical domain knowledge is required to identify representative features in data for detecting a target disease. Most computer scientists and statisticians do not have such domain knowledge. In this work, we show that employing transfer learning can remedy both problems. We use Otitis Media (OM) to conduct our case study. Instead of using domain knowledge to extract features from labeled OM images, we construct features based on a dataset entirely OM-irrelevant. More specifically, we first learn a codebook in an unsupervised way from 15 million images collected from ImageNet. The codebook gives us what the encoders consider being the fundamental elements of those 15 million images. We then encode OM images using the codebook and obtain a weighting vector for each OM image. Using the resulting weighting vectors as the feature vectors of the OM images, we employ a traditional supervised learning algorithm to train an OM classifier. The achieved detection accuracy is 88.5 (89.63 in sensitivity and 86.9 in specificity), markedly higher than all previous attempts, which relied on domain experts to help extract features. Identifying biomarkers with predictive value for disease risk stratification is an important task in epidemiology. This paper describes an application of Bayesian linear survival regression to model cardiovascular event risk in diabetic individuals with measurements available on 55 candidate biomarkers. We extend the survival model to include data from a larger set of non-diabetic individuals in an effort to increase the predictive performance for the diabetic subpopulation. We compare the Gaussian, Laplace and horseshoe shrinkage priors, and find that the last has the best predictive performance and shrinks strong predictors less than the others. We implement the projection predictive covariate selection approach of Dupuis and Robert (2003) to further search for small sets of predictive biomarkers that could provide cost-efficient prediction without significant loss in performance. In passing, we present a derivation of the projective covariate selection in Bayesian decision theoretic framework. Big data bring new opportunities for methods that efficiently summarize and automatically extract knowledge from such compendia. While both supervised learning algorithms and unsupervised clustering algorithms have been successfully applied to biological data, they are either dependent on known biology or limited to discerning the most significant signals in the data. Here we present denoising autoencoders (DAs), which employ a data-defined learning objective independent of known biology, as a method to identify and extract complex patterns from genomic data. We evaluate the performance of DAs by applying them to a large collection of breast cancer gene expression data. Results show that DAs successfully construct features that contain both clinical and molecular information. There are features that represent tumor or normal samples, estrogen receptor (ER) status, and molecular subtypes. Features constructed by the autoencoder generalize to an independent dataset collected using a distinct experimental platform. By integrating data from ENCODE for feature interpretation, we discover a feature representing ER status through association with key transcription factors in breast cancer. We also identify a feature highly predictive of patient survival and it is enriched by FOXM1 signaling pathway. The features constructed by DAs are often bimodally distributed with one peak near zero and another near one, which facilitates discretization. In summary, we demonstrate that DAs effectively extract key biological principles from gene expression data and summarize them into constructed features with convenient properties.