OralImmunoAnalyser: a software tool for immunohistochemical assessment of oral leukoplakia using image segmentation and classification models.

Oral cancer ranks sixteenth amongst types of cancer by number of deaths. Many oral cancers are developed from potentially malignant disorders such as oral leukoplakia, whose most frequent predictor is the presence of epithelial dysplasia. Immunohistochemical staining using cell proliferation biomarkers such as ki67 is a complementary technique to improve the diagnosis and prognosis of oral leukoplakia. The cell counting of these images was traditionally done manually, which is time-consuming and not very reproducible due to intra- and inter-observer variability. The software presently available is not suitable for this task. This article presents the OralImmunoAnalyser software (registered by the University of Santiago de Compostela-USC), which combines automatic image processing with a friendly graphical user interface that allows investigators to oversee and easily correct the automatically recognized cells before quantification. OralImmunoAnalyser is able to count the number of cells in three staining levels and each epithelial layer. Operating in the daily work of the Odontology Faculty, it registered a sensitivity of 64.4% and specificity of 93% for automatic cell detection, with an accuracy of 79.8% for cell classification. Although expert supervision is needed before quantification, OIA reduces the expert analysis time by 56.5% compared to manual counting, avoiding mistakes because the user can check the cells counted. Hence, the SUS questionnaire reported a mean score of 80.9, which means that the system was perceived from good to excellent. OralImmunoAnalyser is accurate, trustworthy, and easy to use in daily practice in biomedical labs. The software, for Windows and Linux, with the images used in this study, can be downloaded from https://citius.usc.es/transferencia/software/oralimmunoanalyser for research purposes upon acceptance.

Software BreastAnalyser for the semi-automatic analysis of breast cancer immunohistochemical images.

Breast cancer is the most diagnosed cancer worldwide and represents the fifth cause of cancer mortality globally. It is a highly heterogeneous disease, that comprises various molecular subtypes, often diagnosed by immunohistochemistry. This technique is widely employed in basic, translational and pathological anatomy research, where it can support the oncological diagnosis, therapeutic decisions and biomarker discovery. Nevertheless, its evaluation is often qualitative, raising the need for accurate quantitation methodologies. We present the software BreastAnalyser, a valuable and reliable tool to automatically measure the area of 3,3'-diaminobenzidine tetrahydrocholoride (DAB)-brown-stained proteins detected by immunohistochemistry. BreastAnalyser also automatically counts cell nuclei and classifies them according to their DAB-brown-staining level. This is performed using sophisticated segmentation algorithms that consider intrinsic image variability and save image normalization time. BreastAnalyser has a clean, friendly and intuitive interface that allows to supervise the quantitations performed by the user, to annotate images and to unify the experts' criteria. BreastAnalyser was validated in representative human breast cancer immunohistochemistry images detecting various antigens. According to the automatic processing, the DAB-brown area was almost perfectly recognized, being the average difference between true and computer DAB-brown percentage lower than 0.7 points for all sets. The detection of nuclei allowed proper cell density relativization of the brown signal for comparison purposes between the different patients. BreastAnalyser obtained a score of 85.5 using the system usability scale questionnaire, which means that the tool is perceived as excellent by the experts. In the biomedical context, the connexin43 (Cx43) protein was found to be significantly downregulated in human core needle invasive breast cancer samples when compared to normal breast, with a trend to decrease as the subtype malignancy increased. Higher Cx43 protein levels were significantly associated to lower cancer recurrence risk in Oncotype DX-tested luminal B HER2- breast cancer tissues. BreastAnalyser and the annotated images are publically available https://citius.usc.es/transferencia/software/breastanalyser for research purposes.

CT-Based Radiomics to Predict KRAS Mutation in CRC Patients Using a Machine Learning Algorithm: A Retrospective Study.

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. The KRAS mutation is present in 30-50% of CRC patients. This mutation confers resistance to treatment with anti-EGFR therapy. This article aims at proving that computer tomography (CT)-based radiomics can predict the KRAS mutation in CRC patients. The piece is a retrospective study with 56 CRC patients from the Hospital of Santiago de Compostela, Spain. All patients had a confirmatory pathological analysis of the KRAS status. Radiomics features were obtained using an abdominal contrast enhancement CT (CECT) before applying any treatments. We used several classifiers, including AdaBoost, neural network, decision tree, support vector machine, and random forest, to predict the presence or absence of KRAS mutation. The most reliable prediction was achieved using the AdaBoost ensemble on clinical patient data, with a kappa and accuracy of 53.7% and 76.8%, respectively. The sensitivity and specificity were 73.3% and 80.8%. Using texture descriptors, the best accuracy and kappa were 73.2% and 46%, respectively, with sensitivity and specificity of 76.7% and 69.2%, also showing a correlation between texture patterns on CT images and KRAS mutation. Radiomics could help manage CRC patients, and in the future, it could have a crucial role in diagnosing CRC patients ahead of invasive methods.

A Machine Learning Approach in Autism Spectrum Disorders: From Sensory Processing to Behavior Problems.

Atypical sensory processing described in autism spectrum disorders (ASDs) frequently cascade into behavioral alterations: isolation, aggression, indifference, anxious/depressed states, or attention problems. Predictive machine learning models might refine the statistical explorations of the associations between them by finding out how these dimensions are related. This study investigates whether behavior problems can be predicted using sensory processing abilities. Participants were 72 children and adolescents (21 females) diagnosed with ASD, aged between 6 and 14 years (M = 7.83 years; SD = 2.80 years). Parents of the participants were invited to answer the Sensory Profile 2 (SP2) and the Child Behavior Checklist (CBCL) questionnaires. A collection of 26 supervised machine learning regression models of different families was developed to predict the CBCL outcomes using the SP2 scores. The most reliable predictions were for the following outcomes: total problems (using the items in the SP2 touch scale as inputs), anxiety/depression (using avoiding quadrant), social problems (registration), and externalizing scales, revealing interesting relations between CBCL outcomes and SP2 scales. The prediction reliability on the remaining outcomes was "moderate to good" except somatic complaints and rule-breaking, where it was "bad to moderate." Linear and ridge regression achieved the best prediction for a single outcome and globally, respectively, and gradient boosting machine achieved the best prediction in three outcomes. Results highlight the utility of several machine learning models in studying the predictive value of sensory processing impairments (with an early onset) on specific behavior alterations, providing evidences of relationship between sensory processing impairments and behavior problems in ASD.

Viability Study of Machine Learning-Based Prediction of COVID-19 Pandemic Impact in Obsessive-Compulsive Disorder Patients.

BACKGROUND: Machine learning modeling can provide valuable support in different areas of mental health, because it enables to make rapid predictions and therefore support the decision making, based on valuable data. However, few studies have applied this method to predict symptoms' worsening, based on sociodemographic, contextual, and clinical data. Thus, we applied machine learning techniques to identify predictors of symptomatologic changes in a Spanish cohort of OCD patients during the initial phase of the COVID-19 pandemic. METHODS: 127 OCD patients were assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and a structured clinical interview during the COVID-19 pandemic. Machine learning models for classification (LDA and SVM) and regression (linear regression and SVR) were constructed to predict each symptom based on patient's sociodemographic, clinical and contextual information. RESULTS: A Y-BOCS score prediction model was generated with 100% reliability at a score threshold of ± 6. Reliability of 100% was reached for obsessions and/or compulsions related to COVID-19. Symptoms of anxiety and depression were predicted with less reliability (correlation R of 0.58 and 0.68, respectively). The suicidal thoughts are predicted with a sensitivity of 79% and specificity of 88%. The best results are achieved by SVM and SVR. CONCLUSION: Our findings reveal that sociodemographic and clinical data can be used to predict changes in OCD symptomatology. Machine learning may be valuable tool for helping clinicians to rapidly identify patients at higher risk and therefore provide optimized care, especially in future pandemics. However, further validation of these models is required to ensure greater reliability of the algorithms for clinical implementation to specific objectives of interest.

Fast Support Vector Classification for Large-Scale Problems.

The support vector machine (SVM) is a very important machine learning algorithm with state-of-the-art performance on many classification problems. However, on large datasets it is very slow and requires much memory. To solve this defficiency, we propose the fast support vector classifier (FSVC) that includes: 1) an efficient closed-form training free of any numerical iterative procedure; 2) a small collection of class prototypes that avoids to store in memory an excessive number of support vectors; and 3) a fast method that selects the spread of the radial basis function kernel directly from data, without classifier execution nor iterative hyper-parameter tuning. The memory requirements of FSVC are very low, spending in average only 6 ·10-7 sec. per pattern, input and class, and processing datasets up to 31 millions of patterns, 30,000 inputs and 131 classes in less than 1.5 hours (less than 3 hours with only 2GB of RAM). In average, the FSVC is 10 times faster, requires 12 times less memory and achieves 4.7 percent more performance than Liblinear, that fails on the 4 largest datasets by lack of memory, being 100 times faster and achieving only 6.7 percent less performance than Libsvm. The time spent by FSVC only depends on the dataset size and thus it can be accurately estimated for new datasets, while Libsvm or Liblinear are much slower on "difficult" datasets, even if they are small. The FSVC adjusts its requirements to the available memory, classifying large datasets in computers with limited memory. Code for the proposed algorithm in the Octave scientific programming language is provided.1.

CystAnalyser: A new software tool for the automatic detection and quantification of cysts in Polycystic Kidney and Liver Disease, and other cystic disorders.

The Polycystic Kidney Disease (PKD) is characterized by progressive renal cyst development and other extrarenal manifestation including Polycystic Liver Disease (PLD). Phenotypical characterization of animal models mimicking human diseases are commonly used, in order to, study new molecular mechanisms and identify new therapeutic approaches. The main biomarker of disease progression is total volume of kidney and liver in both human and mouse, which correlates with organ function. For this reason, the estimation of the number and area of the tissue occupied by cysts, is critical for the understanding of physiological mechanisms underlying the disease. In this regard, cystic index is a robust parameter commonly used to quantify the severity of the disease. To date, the vast majority of biomedical researchers use ImageJ as a software tool to estimate the cystic index by quantifying the cystic areas of histological images after thresholding. This tool has imitations of being inaccurate, largely due to incorrectly identifying non-cystic regions. We have developed a new software, named CystAnalyser (register by Universidade de Santiago de Compostela-USC, and Fundación Investigación Sanitaria de Santiago-FIDIS), that combines automatic image processing with a graphical user friendly interface that allows investigators to oversee and easily correct the image processing before quantification. CystAnalyser was able to generate a cystic profile including cystic index, number of cysts and cyst size. In order to test the CystAnalyser software, 795 cystic kidney, and liver histological images were analyzed. Using CystAnalyser there were no differences calculating cystic index automatically versus user input, except in specific circumstances where it was necessary for the user to distinguish between mildly cystic from non-cystic regions. The sensitivity and specificity of the number of cysts detected by the automatic quantification depends on the type of organ and cystic severity, with values 76.84-78.59% and 76.96-89.66% for the kidney and 87.29-93.80% and 63.42-86.07% for the liver. CystAnalyser, in addition, provides a new tool for estimating the number of cysts and a more specific measure of the cystic index than ImageJ. This study proposes CystAnalyser is a new robust and freely downloadable software tool for analyzing the severity of disease by quantifying histological images of cystic organs for routine biomedical research. CystAnalyser can be downloaded from https://citius.usc.es/transferencia/software/cystanalyser (for Windows and Linux) for research purposes.

Direct Kernel Perceptron (DKP): ultra-fast kernel ELM-based classification with non-iterative closed-form weight calculation.

The Direct Kernel Perceptron (DKP) (Fernández-Delgado et al., 2010) is a very simple and fast kernel-based classifier, related to the Support Vector Machine (SVM) and to the Extreme Learning Machine (ELM) (Huang, Wang, & Lan, 2011), whose α-coefficients are calculated directly, without any iterative training, using an analytical closed-form expression which involves only the training patterns. The DKP, which is inspired by the Direct Parallel Perceptron, (Auer et al., 2008), uses a Gaussian kernel and a linear classifier (perceptron). The weight vector of this classifier in the feature space minimizes an error measure which combines the training error and the hyperplane margin, without any tunable regularization parameter. This weight vector can be translated, using a variable change, to the α-coefficients, and both are determined without iterative calculations. We calculate solutions using several error functions, achieving the best trade-off between accuracy and efficiency with the linear function. These solutions for the α coefficients can be considered alternatives to the ELM with a new physical meaning in terms of error and margin: in fact, the linear and quadratic DKP are special cases of the two-class ELM when the regularization parameter C takes the values C=0 and C=∞. The linear DKP is extremely efficient and much faster (over a vast collection of 42 benchmark and real-life data sets) than 12 very popular and accurate classifiers including SVM, Multi-Layer Perceptron, Adaboost, Random Forest and Bagging of RPART decision trees, Linear Discriminant Analysis, K-Nearest Neighbors, ELM, Probabilistic Neural Networks, Radial Basis Function neural networks and Generalized ART. Besides, despite its simplicity and extreme efficiency, DKP achieves higher accuracies than 7 out of 12 classifiers, exhibiting small differences with respect to the best ones (SVM, ELM, Adaboost and Random Forest), which are much slower. Thus, the DKP provides an easy and fast way to achieve classification accuracies which are not too far from the best one for a given problem. The C and Matlab code of DKP are freely available.

Direct parallel perceptrons (DPPs): fast analytical calculation of the parallel perceptrons weights with margin control for classification tasks.

Parallel perceptrons (PPs) are very simple and efficient committee machines (a single layer of perceptrons with threshold activation functions and binary outputs, and a majority voting decision scheme), which nevertheless behave as universal approximators. The parallel delta (P-Delta) rule is an effective training algorithm, which, following the ideas of statistical learning theory used by the support vector machine (SVM), raises its generalization ability by maximizing the difference between the perceptron activations for the training patterns and the activation threshold (which corresponds to the separating hyperplane). In this paper, we propose an analytical closed-form expression to calculate the PPs' weights for classification tasks. Our method, called Direct Parallel Perceptrons (DPPs), directly calculates (without iterations) the weights using the training patterns and their desired outputs, without any search or numeric function optimization. The calculated weights globally minimize an error function which simultaneously takes into account the training error and the classification margin. Given its analytical and noniterative nature, DPPs are computationally much more efficient than other related approaches (P-Delta and SVM), and its computational complexity is linear in the input dimensionality. Therefore, DPPs are very appealing, in terms of time complexity and memory consumption, and are very easy to use for high-dimensional classification tasks. On real benchmark datasets with two and multiple classes, DPPs are competitive with SVM and other approaches but they also allow online learning and, as opposed to most of them, have no tunable parameters.