Comprehensive disease control in systemic lupus erythematosus.

OBJECTIVES: We evaluated a monocentric SLE cohort in order to assess the frequency of Lupus comprehensive disease control (LupusCDC), a condition defined by the achievement of remission and the absence of damage progression. METHODS: Our longitudinal analysis included SLE patients with 5-years follow-up and at least one visit per year. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and three different remission levels were evaluated (Complete Remission, CR; Clinical remission off-corticosteroids; clinical remission on-corticosteroids). Chronic damage was assessed according to SLICC Damage Index (SDI). LupusCDC was defined as remission achievement for at least one year plus absence of chronic damage progression in the previous one year. A machine learning based analysis was carried out, applying and comparing Nonlinear Support Vector Machines (SVM) models and Decision Trees (DT), whereas features ranking was performed with the ReliefF algorithm. RESULTS: We evaluated 172 patients [M/F 16/156, median age 49 years (IQR 16.7), median disease duration 180 months (IQR 156)]. SDI values (baseline mean±SD 0.7 ± 1.1) significantly increased during the follow-up period. In all time-points analyzed, LupusCDC including CR was the most frequently detected. The failure to reach this condition was significantly associated with renal involvement and with the intake of immunosuppressant drugs and glucocorticoid (GC). Ten patients (5.8%) have maintained LupusCDC during the whole 5-year follow-up: these patients had never presented renal involvement and showed lower prevalence of anti-phospholipid antibodies (p = 0.0001). Finally, the prevalence of GC intake was significantly lower (p = 0.0001). The application of machine learning models showed that the available features were able to provide significant information to build predictive models with an AUC score of 0.703 ± 0.02 for DT and 0.713 ± 0.02 for SVM. CONCLUSIONS: Our data on a monocentric cohort suggest that the LupusCDC can efficaciously merge into one outcome SLE-related disease activity and chronic damage in order to perform an all-around evaluation of SLE patients.

Modeling cancer drug response through drug-specific informative genes.

Recent advances in pharmacogenomics have generated a wealth of data of different types whose analysis have helped in the identification of signatures of different cellular sensitivity/resistance responses to hundreds of chemical compounds. Among the different data types, gene expression has proven to be the more successful for the inference of drug response in cancer cell lines. Although effective, the whole transcriptome can introduce noise in the predictive models, since specific mechanisms are required for different drugs and these realistically involve only part of the proteins encoded in the genome. We analyzed the pharmacogenomics data of 961 cell lines tested with 265 anti-cancer drugs and developed different machine learning approaches for dissecting the genome systematically and predict drug responses using both drug-unspecific and drug-specific genes. These methodologies reach better response predictions for the vast majority of the screened drugs using tens to few hundreds genes specific to each drug instead of the whole genome, thus allowing a better understanding and interpretation of drug-specific response mechanisms which are not necessarily restricted to the drug known targets.

Correction: Biomarkers of erosive arthritis in systemic lupus erythematosus: Application of machine learning models.

[This corrects the article DOI: 10.1371/journal.pone.0207926.].

Biomarkers of erosive arthritis in systemic lupus erythematosus: Application of machine learning models.

OBJECTIVE: Limited evidences are available on biomarkers to recognize Systemic Lupus erythematosus (SLE) patients at risk to develop erosive arthritis. Anti-citrullinated peptide antibodies (ACPA) have been widely investigated and identified in up to 50% of X-ray detected erosive arthritis; conversely, few studies evaluated anti-carbamylated proteins antibodies (anti-CarP). Here, we considered the application of machine learning models to identify relevant factors in the development of ultrasonography (US)-detected erosive damage in a large cohort of SLE patients with joint involvement. METHODS: We enrolled consecutive SLE patients with arthritis/arthralgia. All patients underwent joint (DAS28, STR) and laboratory assessment (detection of ACPA, anti-CarP, Rheumatoid Factor, SLE-related antibodies). The bone surfaces of metacarpophalangeal and proximal interphalangeal joints were assessed by US: the presence of erosions was registered with a dichotomous value (0/1), obtaining a total score (0-20). Concerning machine learning techniques, we applied and compared Logistic Regression and Decision Trees in conjunction with the feature selection Forward Wrapper method. RESULTS: We enrolled 120 SLE patients [M/F 8/112, median age 47.0 years (IQR 15.0); median disease duration 120.0 months (IQR 156.0)], 73.3% of them referring at least one episode of arthritis. Erosive damage was identified in 25.8% of patients (mean±SD 0.7±1.6), all of them with clinically evident arthritis. We applied Logistic Regression in conjunction with the Forward Wrapper method, obtaining an AUC value of 0.806±0.02. As a result of the learning procedure, we evaluated the relevance of the different factors: this value was higher than 35% for ACPA and anti-CarP. CONCLUSION: The application of Machine Learning Models allowed to identify factors associated with US-detected erosive bone damage in a large SLE cohort and their relevance in determining this phenotype. Although the scope of this study is limited by the small sample size and its cross-sectional nature, the results suggest the relevance of ACPA and anti-CarP antibodies in the development of erosive damage as also pointed out in other studies.

Prediction of chronic damage in systemic lupus erythematosus by using machine-learning models.

OBJECTIVE: The increased survival in Systemic Lupus Erythematosus (SLE) patients implies the development of chronic damage, occurring in up to 50% of cases. Its prevention is a major goal in the SLE management. We aimed at predicting chronic damage in a large monocentric SLE cohort by using neural networks. METHODS: We enrolled 413 SLE patients (M/F 30/383; mean age ± SD 46.3±11.9 years; mean disease duration ± SD 174.6 ± 112.1 months). Chronic damage was assessed by the SLICC/ACR Damage Index (SDI). We applied Recurrent Neural Networks (RNNs) as a machine-learning model to predict the risk of chronic damage. The clinical data sequences registered for each patient during the follow-up were used for building and testing the RNNs. RESULTS: At the first visit in the Lupus Clinic, 35.8% of patients had an SDI≥1. For the RNN model, two groups of patients were analyzed: patients with SDI = 0 at the baseline, developing damage during the follow-up (N = 38), and patients without damage (SDI = 0). We created a mathematical model with an AUC value of 0.77, able to predict damage development. A threshold value of 0.35 (sensitivity 0.74, specificity 0.76) seemed able to identify patients at risk to develop damage. CONCLUSION: We applied RNNs to identify a prediction model for SLE chronic damage. The use of the longitudinal data from the Sapienza Lupus Cohort, including laboratory and clinical items, resulted able to construct a mathematical model, potentially identifying patients at risk to develop damage.

An Optimization-Based Method for Feature Ranking in Nonlinear Regression Problems.

In this paper, we consider the feature ranking problem, where, given a set of training instances, the task is to associate a score with the features in order to assess their relevance. Feature ranking is a very important tool for decision support systems, and may be used as an auxiliary step of feature selection to reduce the high dimensionality of real-world data. We focus on regression problems by assuming that the process underlying the generated data can be approximated by a continuous function (for instance, a feedforward neural network). We formally state the notion of relevance of a feature by introducing a minimum zero-norm inversion problem of a neural network, which is a nonsmooth, constrained optimization problem. We employ a concave approximation of the zero-norm function, and we define a smooth, global optimization problem to be solved in order to assess the relevance of the features. We present the new feature ranking method based on the solution of instances of the global optimization problem depending on the available training data. Computational experiments on both artificial and real data sets are performed, and point out that the proposed feature ranking method is a valid alternative to existing methods in terms of effectiveness. The obtained results also show that the method is costly in terms of CPU time, and this may be a limitation in the solution of large-dimensional problems.

Intracranial pressure wave morphological classification: automated analysis and clinical validation.

BACKGROUND: Recently, different software has been developed to automatically analyze multiple intracranial pressure (ICP) parameters, but the suggested methods are frequently complex and have no clinical correlation. The objective of this study was to assess the clinical value of a new morphological classification of the cerebrospinal fluid pulse pressure waveform (CSFPPW), comparing it to the elastance index (EI) and CSF-outflow resistance (Rout), and to test the efficacy of an automatic ICP analysis. METHODS: An artificial neural network (ANN) was trained to classify 60 CSFPPWs in four different classes, according to their morphology, and its efficacy was compared to an expert examiner's classification. The morphology of CSFPPW, recorded in 60 patients at baseline, was compared to EI and Rout calculated at the end of an intraventricular infusion test to validate the utility of the proposed classification in patients' clinical evaluation. RESULTS: The overall concordance in CSFPPW classification between the expert examiner and the ANN was 88.3 %. An elevation of EI was statistically related to morphological class' progression. All patients showing pathological baseline CSFPPW (class IV) revealed an alteration of CSF hydrodynamics at the end of their infusion test. CONCLUSIONS: The proposed morphological classification estimates the global ICP wave and its ability to reflect or predict an alteration in CSF hydrodynamics. An ANN can be trained to efficiently recognize four different CSF wave morphologies. This classification seems helpful and accurate for diagnostic use.

Decomposition Techniques for Multilayer Perceptron Training.

In this paper, we consider the learning problem of multilayer perceptrons (MLPs) formulated as the problem of minimizing a smooth error function. As well known, the learning problem of MLPs can be a difficult nonlinear nonconvex optimization problem. Typical difficulties can be the presence of extensive flat regions and steep sided valleys in the error surface, and the possible large number of training data and of free network parameters. We define a wide class of batch learning algorithms for MLP, based on the use of block decomposition techniques in the minimization of the error function. The learning problem is decomposed into a sequence of smaller and structured minimization problems in order to advantageously exploit the structure of the objective function. Theoretical convergence results are established, and a specific algorithm is constructed and evaluated through an extensive numerical experimentation. The comparisons with the state-of-the-art learning algorithms show the effectiveness of the proposed techniques.

Real-time epileptic seizure prediction using AR models and support vector machines.

This paper addresses the prediction of epileptic seizures from the online analysis of EEG data. This problem is of paramount importance for the realization of monitoring/control units to be implanted on drug-resistant epileptic patients. The proposed solution relies in a novel way on autoregressive modeling of the EEG time series and combines a least-squares parameter estimator for EEG feature extraction along with a support vector machine (SVM) for binary classification between preictal/ictal and interictal states. This choice is characterized by low computational requirements compatible with a real-time implementation of the overall system. Moreover, experimental results on the Freiburg dataset exhibited correct prediction of all seizures (100 % sensitivity) and, due to a novel regularization of the SVM classifier based on the Kalman filter, also a low false alarm rate.

A convergent hybrid decomposition algorithm model for SVM training.

Training of support vector machines (SVMs) requires to solve a linearly constrained convex quadratic problem. In real applications, the number of training data may be very huge and the Hessian matrix cannot be stored. In order to take into account this issue, a common strategy consists in using decomposition algorithms which at each iteration operate only on a small subset of variables, usually referred to as the working set. Training time can be significantly reduced by using a caching technique that allocates some memory space to store the columns of the Hessian matrix corresponding to the variables recently updated. The convergence properties of a decomposition method can be guaranteed by means of a suitable selection of the working set and this can limit the possibility of exploiting the information stored in the cache. We propose a general hybrid algorithm model which combines the capability of producing a globally convergent sequence of points with a flexible use of the information in the cache. As an example of a specific realization of the general hybrid model, we describe an algorithm based on a particular strategy for exploiting the information deriving from a caching technique. We report the results of computational experiments performed by simple implementations of this algorithm. The numerical results point out the potentiality of the approach.