Theoretical Interpretations and Applications of Radial Basis Function Networks

Medical applications usually used Radial Basis Function Networks just as Artificial Neural Networks. However, RBFNs are Knowledge-Based Networks that can be interpreted in several way: Artificial Neural Networks, Regularization Networks, Support Vector Machines, Wavelet Networks, Fuzzy Controllers, Kernel Estimators, Instanced-Based Learners. A survey of their interpretations and of their corresponding learning algorithms is provided as well as a brief survey on dynamic learning algorithms. RBFNs' interpretations can suggest applications that are particularly interesting in medical domains

Classification of clinical outcomes using high-throughput and clinical informatics.

It is widely recognized that many cancer therapies are effective only for a subset of patients. However clinical studies are most often powered to detect an overall treatment effect. To address this issue, classification methods are increasingly being used to predict a subset of patients which respond differently to treatment. This study begins with a brief history of classification methods with an emphasis on applications involving melanoma. Nonparametric methods suitable for predicting subsets of patients responding differently to treatment are then reviewed. Each method has different ways of incorporating continuous, categorical, clinical and high-throughput covariates. For nonparametric and parametric methods, distance measures specific to the method are used to make classification decisions. Approaches are outlined which employ these distances to measure treatment interactions and predict patients more sensitive to treatment. Simulations are also carried out to examine empirical power of some of these classification methods in an adaptive signature design. Results were compared with logistic regression models. It was found that parametric and nonparametric methods performed reasonably well. Relative performance of the methods depends on the simulation scenario. Finally a method was developed to evaluate power and sample size needed for an adaptive signature design in order to predict the subset of patients sensitive to treatment. It is hoped that this study will stimulate more development of nonparametric and parametric methods to predict subsets of patients responding differently to treatment

Statistical methods for tissue array images - algorithmic scoring and co-training

Recent advances in tissue microarray technology have allowed immunohistochemistry to become a powerful medium-to-high throughput analysis tool, particularly for the validation of diagnostic and prognostic biomarkers. However, as study size grows, the manual evaluation of these assays becomes a prohibitive limitation; it vastly reduces throughput and greatly increases variability and expense. We propose an algorithm - Tissue Array Co-Occurrence Matrix Analysis (TACOMA) - for quantifying cellular phenotypes based on textural regularity summarized by local inter-pixel relationships. The algorithm can be easily trained for any staining pattern, is absent of sensitive tuning parameters and has the ability to report salient pixels in an image that contribute to its score. Pathologists' input via informative training patches is an important aspect of the algorithm that allows the training for any specific marker or cell type. With co-training, the error rate of TACOMA can be reduced substantially for a very small training sample (e.g., with size 30). We give theoretical insights into the success of co-training via thinning of the feature set in a high-dimensional setting when there is "sufficient" redundancy among the features. TACOMA is flexible, transparent and provides a scoring process that can be evaluated with clarity and confidence. In a study based on an estrogen receptor (ER) marker, we show that TACOMA is comparable to, or outperforms, pathologists' performance in terms of accuracy and repeatability.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS543 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Six skin diseases classification using deep convolutional neural network

Smart imaging-based medical classification systems help the human diagnose the diseases and make better decisions about patient health. Recently, computer-aided classification of skin diseases has been a popular research area due to its importance in the early detection of skin diseases. This paper presents at its core, a system that exploits convolutional neural networks to classify color images of skin lesions. It relies on a pre-trained deep convolutional neural network to classify between six skin diseases: acne, athlete’s foot, chickenpox, eczema, skin cancer, and vitiligo. Additionally, we constructed a dataset of 3000 colored images from several online datasets and the Internet. Experimental results are encouraging, where the proposed model achieved an accuracy of 81.75%, which is higher than the state of the art researches in this field. This accuracy was calculated using the holdout method, where 90% of the images were used for training, and 10% of the images were used for out-of-sample accuracy testing

Methods for Predicting an Ordinal Response with High-Throughput Genomic Data

Multigenic diagnostic and prognostic tools can be derived for ordinal clinical outcomes using data from high-throughput genomic experiments. A challenge in this setting is that the number of predictors is much greater than the sample size, so traditional ordinal response modeling techniques must be exchanged for more specialized approaches. Existing methods perform well on some datasets, but there is room for improvement in terms of variable selection and predictive accuracy. Therefore, we extended an impressive binary response modeling technique, Feature Augmentation via Nonparametrics and Selection, to the ordinal response setting. Through simulation studies and analyses of high-throughput genomic datasets, we showed that our Ordinal FANS method is sensitive and specific when discriminating between important and unimportant features from the high-dimensional feature space and is highly competitive in terms of predictive accuracy. Discrete survival time is another example of an ordinal response. For many illnesses and chronic conditions, it is impossible to record the precise date and time of disease onset or relapse. Further, the HIPPA Privacy Rule prevents recording of protected health information which includes all elements of dates (except year), so in the absence of a “limited dataset,” date of diagnosis or date of death are not available for calculating overall survival. Thus, we developed a method that is suitable for modeling high-dimensional discrete survival time data and assessed its performance by conducting a simulation study and by predicting the discrete survival times of acute myeloid leukemia patients using a high-dimensional dataset

Self-paced balance learning for clinical skin disease recognition

Class imbalance is a challenging problem in many classification tasks. It induces biased classification results for minority classes that contain less training samples than others. Most existing approaches aim to remedy the imbalanced number of instances among categories by resampling the majority and minority classes accordingly. However, the imbalanced level of difficulty of recognizing different categories is also crucial, especially for distinguishing samples with many classes. For example, in the task of clinical skin disease recognition, several rare diseases have a small number of training samples, but they are easy to diagnose because of their distinct visual properties. On the other hand, some common skin diseases, e.g., eczema, are hard to recognize due to the lack of special symptoms. To address this problem, we propose a self-paced balance learning (SPBL) algorithm in this paper. Specifically, we introduce a comprehensive metric termed the complexity of image category that is a combination of both sample number and recognition difficulty. First, the complexity is initialized using the model of the first pace, where the pace indicates one iteration in the self-paced learning paradigm. We then assign each class a penalty weight that is larger for more complex categories and smaller for easier ones, after which the curriculum is reconstructed by rearranging the training samples. Consequently, the model can iteratively learn discriminative representations via balancing the complexity in each pace. Experimental results on the SD-198 and SD-260 benchmark data sets demonstrate that the proposed SPBL algorithm performs favorably against the state-of-the-art methods. We also demonstrate the effectiveness of the SPBL algorithm's generalization capacity on various tasks, such as indoor scene image recognition and object classification

A privacy preserving online learning framework for medical diagnosis applications

Electronic Health records are an important part of a digital healthcare system. Due to their significance, electronic health records have become a major target for hackers, and hospitals/clinics prefer to keep the records at local sites protected by adequate security measures. This introduces challenges in sharing health records. Sharing health records however, is critical in building an accurate online diagnosis framework. Most local sites have small data sets, and machine learning models developed locally based on small data sets, do not have knowledge about other data sets and learning models used at other sites. The work in this thesis utilizes the framework of coordinating the blockchain technology and online training mechanism in order to address the concerns of privacy and security in a methodical manner. Specifically, it integrates online learning with a permissioned blockchain network, using transaction metadata to broadcast a part of models while keeping patient health information private. This framework can treat different types of machine learning models using the same distributed dataset. The study also outlines the advantages and drawbacks of using blockchain technology to tackle the privacy-preserving predictive modeling problem and to improve interoperability amongst institutions. This study implements the proposed solutions for skin cancer diagnosis as a representative case and shows promising results in preserving security and providing high detection accuracy. The experimentation was done on ISIC dataset, and the results were 98.57, 99.13, 99.17 and 97,18 in terms of precision, accuracy, F1-score and recall, respectively

Methods for Predicting an Ordinal Response with High-Throughput Genomic Data

Multigenic diagnostic and prognostic tools can be derived for ordinal clinical outcomes using data from high-throughput genomic experiments. A challenge in this setting is that the number of predictors is much greater than the sample size, so traditional ordinal response modeling techniques must be exchanged for more specialized approaches. Existing methods perform well on some datasets, but there is room for improvement in terms of variable selection and predictive accuracy. Therefore, we extended an impressive binary response modeling technique, Feature Augmentation via Nonparametrics and Selection, to the ordinal response setting. Through simulation studies and analyses of high-throughput genomic datasets, we showed that our Ordinal FANS method is sensitive and specific when discriminating between important and unimportant features from the high-dimensional feature space and is highly competitive in terms of predictive accuracy. Discrete survival time is another example of an ordinal response. For many illnesses and chronic conditions, it is impossible to record the precise date and time of disease onset or relapse. Further, the HIPPA Privacy Rule prevents recording of protected health information which includes all elements of dates (except year), so in the absence of a “limited dataset,” date of diagnosis or date of death are not available for calculating overall survival. Thus, we developed a method that is suitable for modeling high-dimensional discrete survival time data and assessed its performance by conducting a simulation study and by predicting the discrete survival times of acute myeloid leukemia patients using a high-dimensional dataset

Diagnóstico automático de melanoma mediante técnicas modernas de aprendizaje automático

The incidence and mortality rates of skin cancer remain a huge concern in many countries. According to the latest statistics about melanoma skin cancer, only in the Unites States, 7,650 deaths are expected in 2022, which represents 800 and 470 more deaths than 2020 and 2021, respectively. In 2022, melanoma is ranked as the fifth cause of new cases of cancer, with a total of 99,780 people. This illness is mainly diagnosed with a visual inspection of the skin, then, if doubts remain, a dermoscopic analysis is performed. The development of e_ective non-invasive diagnostic tools for the early stages of the illness should increase quality of life, and decrease the required economic resources. The early diagnosis of skin lesions remains a tough task even for expert dermatologists because of the complexity, variability, dubiousness of the symptoms, and similarities between the different categories among skin lesions. To achieve this goal, previous works have shown that early diagnosis from skin images can benefit greatly from using computational methods. Several studies have applied handcrafted-based methods on high quality dermoscopic and histological images, and on top of that, machine learning techniques, such as the k-nearest neighbors approach, support vector machines and random forest. However, one must bear in mind that although the previous extraction of handcrafted features incorporates an important knowledge base into the analysis, the quality of the extracted descriptors relies heavily on the contribution of experts. Lesion segmentation is also performed manually. The above procedures have a common issue: they are time-consuming manual processes prone to errors. Furthermore, an explicit definition of an intuitive and interpretable feature is hardly achievable, since it depends on pixel intensity space and, therefore, they are not invariant regarding the differences in the input images. On the other hand, the use of mobile devices has sharply increased, which offers an almost unlimited source of data. In the past few years, more and more attention has been paid to designing deep learning models for diagnosing melanoma, more specifically Convolutional Neural Networks. This type of model is able to extract and learn high-level features from raw images and/or other data without the intervention of experts. Several studies showed that deep learning models can overcome handcrafted-based methods, and even match the predictive performance of dermatologists. The International Skin Imaging Collaboration encourages the development of methods for digital skin imaging. Every year since 2016 to 2019, a challenge and a conference have been organized, in which more than 185 teams have participated. However, convolutional models present several issues for skin diagnosis. These models can fit on a wide diversity of non-linear data points, being prone to overfitting on datasets with small numbers of training examples per class and, therefore, attaining a poor generalization capacity. On the other hand, this type of model is sensitive to some characteristics in data, such as large inter-class similarities and intra-class variances, variations in viewpoints, changes in lighting conditions, occlusions, and background clutter, which can be mostly found in non-dermoscopic images. These issues represent challenges for the application of automatic diagnosis techniques in the early phases of the illness. As a consequence of the above, the aim of this Ph.D. thesis is to make significant contributions to the automatic diagnosis of melanoma. The proposals aim to avoid overfitting and improve the generalization capacity of deep models, as well as to achieve a more stable learning and better convergence. Bear in mind that research into deep learning commonly requires an overwhelming processing power in order to train complex architectures. For example, when developing NASNet architecture, researchers used 500 x NVidia P100s - each graphic unit cost from $5,899 to$7,374, which represents a total of $2,949,500.00 -$3,687,000.00. Unfortunately, the majority of research groups do not have access to such resources, including ours. In this Ph.D. thesis, the use of several techniques has been explored. First, an extensive experimental study was carried out, which included state-of-the-art models and methods to further increase the performance. Well-known techniques were applied, such as data augmentation and transfer learning. Data augmentation is performed in order to balance out the number of instances per category and act as a regularizer in preventing overfitting in neural networks. On the other hand, transfer learning uses weights of a pre-trained model from another task, as the initial condition for the learning of the target network. Results demonstrate that the automatic diagnosis of melanoma is a complex task. However, different techniques are able to mitigate such issues in some degree. Finally, suggestions are given about how to train convolutional models for melanoma diagnosis and future interesting research lines were presented. Next, the discovery of ensemble-based architectures is tackled by using genetic algorithms. The proposal is able to stabilize the training process. This is made possible by finding sub-optimal combinations of abstract features from the ensemble, which are used to train a convolutional block. Then, several predictive blocks are trained at the same time, and the final diagnosis is achieved by combining all individual predictions. We empirically investigate the benefits of the proposal, which shows better convergence, mitigates the overfitting of the model, and improves the generalization performance. On top of that, the proposed model is available online and can be consulted by experts. The next proposal is focused on designing an advanced architecture capable of fusing classical convolutional blocks and a novel model known as Dynamic Routing Between Capsules. This approach addresses the limitations of convolutional blocks by using a set of neurons instead of an individual neuron in order to represent objects. An implicit description of the objects is learned by each capsule, such as position, size, texture, deformation, and orientation. In addition, a hyper-tuning of the main parameters is carried out in order to ensure e_ective learning under limited training data. An extensive experimental study was conducted where the fusion of both methods outperformed six state-of-the-art models. On the other hand, a robust method for melanoma diagnosis, which is inspired on residual connections and Generative Adversarial Networks, is proposed. The architecture is able to produce plausible photorealistic synthetic 512 x 512 skin images, even with small dermoscopic and non-dermoscopic skin image datasets as problema domains. In this manner, the lack of data, the imbalance problems, and the overfitting issues are tackled. Finally, several convolutional modes are extensively trained and evaluated by using the synthetic images, illustrating its effectiveness in the diagnosis of melanoma. In addition, a framework, which is inspired on Active Learning, is proposed. The batch-based query strategy setting proposed in this work enables a more faster training process by learning about the complexity of the data. Such complexities allow us to adjust the training process after each epoch, which leads the model to achieve better performance in a lower number of iterations compared to random mini-batch sampling. Then, the training method is assessed by analyzing both the informativeness value of each image and the predictive performance of the models. An extensive experimental study is conducted, where models trained with the proposal attain significantly better results than the baseline models. The findings suggest that there is still space for improvement in the diagnosis of skin lesions. Structured laboratory data, unstructured narrative data, and in some cases, audio or observational data, are given by radiologists as key points during the interpretation of the prediction. This is particularly true in the diagnosis of melanoma, where substantial clinical context is often essential. For example, symptoms like itches and several shots of a skin lesion during a period of time proving that the lesion is growing, are very likely to suggest cancer. The use of different types of input data could help to improve the performance of medical predictive models. In this regard, a _rst evolutionary algorithm aimed at exploring multimodal multiclass data has been proposed, which surpassed a single-input model. Furthermore, the predictive features extracted by primary capsules could be used to train other models, such as Support Vector Machine