Identifying multiple sclerosis subtypes using unsupervised machine learning and MRI data.
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ABSTRACT:
SUBMITTER: Eshaghi A
PROVIDER: S-EPMC8024377 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTo stratify patients with multiple sclerosis (pwMS) based on brain MRI-derived volumetric features using unsupervised machine learning.MethodsThe 3-T brain MRIs of relapsing-remitting pwMS including 3D-T1w and FLAIR-T2w sequences were retrospectively collected, along with Expanded Disability Status Scale (EDSS) scores and long-term (10 ± 2 years) clinical outcomes (EDSS, cognition, and progressive course). From the MRIs, volumes of demyelinating lesions and 116 atlas-defined gray matter regions were automatically segmented and expressed as z-scores referenced to external populations. Following feature selection, baseline MRI-derived biomarkers entered the Subtype and Stage Inference (SuStaIn) algorithm, which estimates subgroups characterized by distinct patterns of biomarker evolution and stages within subgroups. The trained model was then applied to longitudinal MRIs. Stability of subtypes and stage change over time were assessed via Krippendorf's α and multilevel linear regression models, respectively. The prognostic relevance of SuStaIn classification was assessed with ordinal/logistic regression analyses.ResultsWe selected 425 pwMS (35.9 ± 9.9 years; F/M: 301/124), corresponding to 1129 MRI scans, along with healthy controls (N = 148; 35.9 ± 13.0 years; F/M: 77/71) and external pwMS (N = 80; 40.4 ± 11.9 years; F/M: 56/24) as reference populations. Based on 11 biomarkers surviving feature selection, two subtypes were identified, designated as "deep gray matter (DGM)-first" subtype (N = 238) and "cortex-first" subtype (N = 187) according to the atrophy pattern. Subtypes were consistent over time (α = 0.806), with significant annual stage increase (b = 0.20; p < 0.001). EDSS was associated with stage and DGM-first subtype (p ≤ 0.02). Baseline stage predicted long-term disability, transition to progressive course, and cognitive impairment (p ≤ 0.03), with the latter also associated with DGM-first subtype (p = 0.005).ConclusionsUnsupervised learning modelling of brain MRI-derived volumetric features provides a biologically reliable and prognostically meaningful stratification of pwMS.Key points• The unsupervised modelling of brain MRI-derived volumetric features can provide a single-visit stratification of multiple sclerosis patients. • The so-obtained classification tends to be consistent over time and captures disease-related brain damage progression, supporting the biological reliability of the model. • Baseline stratification predicts long-term clinical disability, cognition, and transition to secondary progressive course.
| S-EPMC9279232 | biostudies-literature
Project description:BackgroundIdentifying active lesions in magnetic resonance imaging (MRI) is crucial for the diagnosis and treatment planning of multiple sclerosis (MS). Active lesions on MRI are identified following the administration of Gadolinium-based contrast agents (GBCAs). However, recent studies have reported that repeated administration of GBCA results in the accumulation of Gd in tissues. In addition, GBCA administration increases health care costs. Thus, reducing or eliminating GBCA administration for active lesion detection is important for improved patient safety and reduced healthcare costs. Current state-of-the-art methods for identifying active lesions in brain MRI without GBCA administration utilize data-intensive deep learning methods.ObjectiveTo implement nonlinear dimensionality reduction (NLDR) methods, locally linear embedding (LLE) and isometric feature mapping (Isomap), which are less data-intensive, for automatically identifying active lesions on brain MRI in MS patients, without the administration of contrast agents.Materials and methodsFluid-attenuated inversion recovery (FLAIR), T2-weighted, proton density-weighted, and pre- and post-contrast T1-weighted images were included in the multiparametric MRI dataset used in this study. Subtracted pre- and post-contrast T1-weighted images were labeled by experts as active lesions (ground truth). Unsupervised methods, LLE and Isomap, were used to reconstruct multiparametric brain MR images into a single embedded image. Active lesions were identified on the embedded images and compared with ground truth lesions. The performance of NLDR methods was evaluated by calculating the Dice similarity (DS) index between the observed and identified active lesions in embedded images.ResultsLLE and Isomap, were applied to 40 MS patients, achieving median DS scores of 0.74 ± 0.1 and 0.78 ± 0.09, respectively, outperforming current state-of-the-art methods.ConclusionsNLDR methods, Isomap and LLE, are viable options for the identification of active MS lesions on non-contrast images, and potentially could be used as a clinical decision tool.
| S-EPMC10969435 | biostudies-literature
Project description:BackgroundAlzheimer's disease (AD) is a highly heterogeneous disease with diverse trajectories and outcomes observed in clinical populations. Understanding this heterogeneity can enable better treatment, prognosis and disease management. Studies to date have mainly used imaging or cognition data and have been limited in terms of data breadth and sample size. Here we examine the clinical heterogeneity of Alzheimer's disease patients using electronic health records (EHR) to identify and characterise disease subgroups using multiple clustering methods, identifying clusters which are clinically actionable.MethodsWe identified AD patients in primary care EHR from the Clinical Practice Research Datalink (CPRD) using a previously validated rule-based phenotyping algorithm. We extracted and included a range of comorbidities, symptoms and demographic features as patient features. We evaluated four different clustering methods (k-means, kernel k-means, affinity propagation and latent class analysis) to cluster Alzheimer's disease patients. We compared clusters on clinically relevant outcomes and evaluated each method using measures of cluster structure, stability, efficiency of outcome prediction and replicability in external data sets.ResultsWe identified 7,913 AD patients, with a mean age of 82 and 66.2% female. We included 21 features in our analysis. We observed 5, 2, 5 and 6 clusters in k-means, kernel k-means, affinity propagation and latent class analysis respectively. K-means was found to produce the most consistent results based on four evaluative measures. We discovered a consistent cluster found in three of the four methods composed of predominantly female, younger disease onset (43% between ages 42-73) diagnosed with depression and anxiety, with a quicker rate of progression compared to the average across other clusters.ConclusionEach clustering approach produced substantially different clusters and K-Means performed the best out of the four methods based on the four evaluative criteria. However, the consistent appearance of one particular cluster across three of the four methods potentially suggests the presence of a distinct disease subtype that merits further exploration. Our study underlines the variability of the results obtained from different clustering approaches and the importance of systematically evaluating different approaches for identifying disease subtypes in complex EHR.
| S-EPMC8653614 | biostudies-literature
Project description:BackgroundMultiple sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging and multimodal biomarkers to define the risk of disease activity.MethodsWe have analysed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centres, collecting disability scales at baseline and 2 years later. Imaging data included brain MRI and optical coherence tomography, and omics included genotyping, cytomics and phosphoproteomic data from peripheral blood mononuclear cells. Predictors of clinical outcomes were searched using Random Forest algorithms. Assessment of the algorithm performance was conducted in an independent prospective cohort of 271 MS patients from a single centre.ResultsWe found algorithms for predicting confirmed disability accumulation for the different scales, no evidence of disease activity (NEDA), onset of immunotherapy and the escalation from low- to high-efficacy therapy with intermediate to high-accuracy. This accuracy was achieved for most of the predictors using clinical data alone or in combination with imaging data. Still, in some cases, the addition of omics data slightly increased algorithm performance. Accuracies were comparable in both cohorts.ConclusionCombining clinical, imaging and omics data with machine learning helps identify MS patients at risk of disability worsening.
| S-EPMC10896787 | biostudies-literature
Project description:Multiple sclerosis (MS) is a multifaceted neurological condition characterized by challenges in timely diagnosis and personalized patient management. The application of Artificial Intelligence (AI) to MS holds promises for early detection, accurate diagnosis, and predictive modeling. The objectives of this study are: 1) to propose new MS trajectory descriptors that could be employed in Machine Learning (ML) regressors and classifiers to predict patient evolution; 2) to explore the contribution of ML models in discerning MS trajectory descriptors using only baseline Magnetic Resonance Imaging (MRI) studies. This study involved 446 MS patients who had a baseline MRI, at least two measurements of Expanded Disability Status Scale (EDSS), and a 1-year follow-up. Patients were divided into two groups: 1) for model development and 2) for evaluation. Three descriptors: β1, β2, and EDSS(t), were related to baseline MRI parameters using regression and classification XGBoost models. Shapley Additive Explanations (SHAP) analysis enhanced model transparency by identifying influential features. The results of this study demonstrate the potential of AI in predicting MS progression using the proposed patient trajectories and baseline MRI scans, outperforming classic Multiple Linear Regression (MLR) methods. In conclusion, MS trajectory descriptors are crucial; incorporating AI analysis into MRI assessments presents promising opportunities to advance predictive capabilities. SHAP analysis enhances model interpretation, revealing feature importance for clinical decisions.
| S-EPMC11251627 | biostudies-literature
Project description:We focused on building models that incorporated transcription factor (TF)-DNA interaction data for 12 members of the Auxin Response Factor (ARF) family from soybean as assessed by DNA Affinity Purification and sequencing (DAP-seq).
2023-06-01 | GSE193400 | GEO
Project description:The intervention at the stage of mild cognitive impairment (MCI) is promising for preventing Alzheimer's disease (AD). This study aims to search for the optimal machine learning (ML) model to classify early and late MCI (EMCI and LMCI) subtypes using multimodal MRI data. First, the tract-based spatial statistics (TBSS) analyses showed LMCI-related white matter changes in the Corpus Callosum. The ROI-based tractography addressed the connected cortical areas by affected callosal fibers. We then prepared two feature subsets for ML by measuring resting-state functional connectivity (TBSS-RSFC method) and graph theory metrics (TBSS-Graph method) in these cortical areas, respectively. We also prepared feature subsets of diffusion parameters in the regions of LMCI-related white matter alterations detected by TBSS analyses. Using these feature subsets, we trained and tested multiple ML models for EMCI/LMCI classification with cross-validation. Our results showed the ensemble ML model (AdaBoost) with feature subset of diffusion parameters achieved better performance of mean accuracy 70%. The useful brain regions for classification were those, including frontal, parietal lobe, Corpus Callosum, cingulate regions, insula, and thalamus regions. Our findings indicated the optimal ML model using diffusion parameters might be effective to distinguish LMCI from EMCI subjects at the prodromal stage of AD.
| S-EPMC8917197 | biostudies-literature
Project description:Psychiatric disorders show heterogeneous symptoms and trajectories, with current nosology not accurately reflecting their molecular etiology and the variability and symptomatic overlap within and between diagnostic classes. This heterogeneity impedes timely and targeted treatment. Our study aimed to identify psychiatric patient clusters that share clinical and genetic features and may profit from similar therapies. We used high-dimensional data clustering on deep clinical data to identify transdiagnostic groups in a discovery sample (N = 1250) of healthy controls and patients diagnosed with depression, bipolar disorder, schizophrenia, schizoaffective disorder, and other psychiatric disorders. We observed five diagnostically mixed clusters and ordered them based on severity. The least impaired cluster 0, containing most healthy controls, showed general well-being. Clusters 1-3 differed predominantly regarding levels of maltreatment, depression, daily functioning, and parental bonding. Cluster 4 contained most patients diagnosed with psychotic disorders and exhibited the highest severity in many dimensions, including medication load. Depressed patients were present in all clusters, indicating that we captured different disease stages or subtypes. We replicated all but the smallest cluster 1 in an independent sample (N = 622). Next, we analyzed genetic differences between clusters using polygenic scores (PGS) and the psychiatric family history. These genetic variables differed mainly between clusters 0 and 4 (prediction area under the receiver operating characteristic curve (AUC) = 81%; significant PGS: cross-disorder psychiatric risk, schizophrenia, and educational attainment). Our results confirm that psychiatric disorders consist of heterogeneous subtypes sharing molecular factors and symptoms. The identification of transdiagnostic clusters advances our understanding of the heterogeneity of psychiatric disorders and may support the development of personalized treatments.
| S-EPMC8429672 | biostudies-literature
Project description:To assess the possible utility of machine learning for classifying subjects with and subjects without osteoarthritis using sodium magnetic resonance imaging data. Theory: Support vector machine, k-nearest neighbors, naïve Bayes, discriminant analysis, linear regression, logistic regression, neural networks, decision tree, and tree bagging were tested.Sodium magnetic resonance imaging with and without fluid suppression by inversion recovery was acquired on the knee cartilage of 19 controls and 28 osteoarthritis patients. Sodium concentrations were measured in regions of interests in the knee for both acquisitions. Mean (MEAN) and standard deviation (STD) of these concentrations were measured in each regions of interest, and the minimum, maximum, and mean of these two measurements were calculated over all regions of interests for each subject. The resulting 12 variables per subject were used as predictors for classification.Either Min [STD] alone, or in combination with Mean [MEAN] or Min [MEAN], all from fluid suppressed data, were the best predictors with an accuracy >74%, mainly with linear logistic regression and linear support vector machine. Other good classifiers include discriminant analysis, linear regression, and naïve Bayes.Machine learning is a promising technique for classifying osteoarthritis patients and controls from sodium magnetic resonance imaging data.
| S-EPMC4417663 | biostudies-literature
Project description:Automatic segmentation of Multiple Sclerosis (MS) lesions from Magnetic Resonance Imaging (MRI) images is essential for clinical assessment and treatment planning of MS. Recent years have seen an increasing use of Convolutional Neural Networks (CNNs) for this task. Although these methods provide accurate segmentation, their applicability in clinical settings remains limited due to a reproducibility issue across different image domains. MS images can have highly variable characteristics across patients, MRI scanners and imaging protocols; retraining a supervised model with data from each new domain is not a feasible solution because it requires manual annotation from expert radiologists. In this work, we explore an unsupervised solution to the problem of domain shift. We present a framework, Seg-JDOT, which adapts a deep model so that samples from a source domain and samples from a target domain sharing similar representations will be similarly segmented. We evaluated the framework on a multi-site dataset, MICCAI 2016, and showed that the adaptation toward a target site can bring remarkable improvements in a model performance over standard training.
| S-EPMC7075308 | biostudies-literature