Multiclassification of Hepatic Cystic Echinococcosis by Using Multiple Kernel Learning Framework and Ultrasound Images.

To properly treat and care for hepatic cystic echinococcosis (HCE), it is essential to make an accurate diagnosis before treatment. OBJECTIVE: The objective of this study was to assess the diagnostic accuracy of computer-aided diagnosis techniques in classifying HCE ultrasound images into five subtypes. METHODS: A total of 1820 HCE ultrasound images collected from 967 patients were included in the study. A multi-kernel learning method was developed to learn the texture and depth features of the ultrasound images. Combined kernel functions were built-in Support Vector Machine (MK-SVM) for the classification work. The experimental results were evaluated using five-fold cross-validation. Finally, our approach was compared with three other machine learning algorithms: the decision tree classifier, random forest, and gradient boosting decision tree. RESULTS: Among all the methods used in the study, the MK-SVM achieved the highest accuracy of 96.6% on the fused feature set. CONCLUSION: The multi-kernel learning method effectively learns different image features from ultrasound images by utilizing various kernels. The MK-SVM method, which combines the learning of texture features and depth features separately, has significant application value in HCE classification tasks.

Topological properties analysis and identification of mild cognitive impairment based on individual morphological brain network connectome.

Mild cognitive impairment is considered the prodromal stage of Alzheimer's disease. Accurate diagnosis and the exploration of the pathological mechanism of mild cognitive impairment are extremely valuable for targeted Alzheimer's disease prevention and early intervention. In all, 100 mild cognitive impairment patients and 86 normal controls were recruited in this study. We innovatively constructed the individual morphological brain networks and derived multiple brain connectome features based on 3D-T1 structural magnetic resonance imaging with the Jensen-Shannon divergence similarity estimation method. Our results showed that the most distinguishing morphological brain connectome features in mild cognitive impairment patients were consensus connections and nodal graph metrics, mainly located in the frontal, occipital, limbic lobes, and subcortical gray matter nuclei, corresponding to the default mode network. Topological properties analysis revealed that mild cognitive impairment patients exhibited compensatory changes in the frontal lobe, while abnormal cortical-subcortical circuits associated with cognition were present. Moreover, the combination of multidimensional brain connectome features using multiple kernel-support vector machine achieved the best classification performance in distinguishing mild cognitive impairment patients and normal controls, with an accuracy of 84.21%. Therefore, our findings are of significant importance for developing potential brain imaging biomarkers for early detection of Alzheimer's disease and understanding the neuroimaging mechanisms of the disease.

PDATC-NCPMKL: Predicting drug's Anatomical Therapeutic Chemical (ATC) codes based on network consistency projection and multiple kernel learning.

The development and discovery of new drugs is time-consuming and needs lots of human and material resources. Therefore, discovery of novel effects of existing drugs is an important alternative way, which can accelerate the process of designing "new" drugs. The anatomical Therapeutic Chemical (ATC) classification system recommended by World Health Organization (WHO) is a basic research area in this regard. A novel ATC code of an existing drug suggests its novel effects. Some computational models have been proposed, which can predict the drug-ATC code associations. However, their performance is not very high. There still exist spaces for improvement. In this study, a new recommendation system (named PDATC-NCPMKL), which incorporated network consistency projection and multi-kernel learning, was designed to identify drug-ATC code associations. For drugs or ATC codes, several kernels were constructed, which were fused by a multiple kernel learning method and an additional kernel integration scheme. To enhance the performance, the drug-ATC code association adjacency matrix was reformulated by a variant of weighted K nearest known neighbors (WKNKN). The reformulated adjacency matrix, drug and ATC code kernels were fed into network consistency projection to generate the association score matrix. The proposed recommendation system was tested on the ATC codes at the second, third and fourth levels in drug ATC classification system using ten-fold cross-validation. The results indicated that all AUROC and AUPR values were close to or exceeded 0.96. Such performance was higher than some existing computational models. Some additional tests were conducted to prove the utility of adjacency matrix reformulation and to analyze the importance of drug and ATC code kernels.

Identification of DNA-binding protein based multiple kernel model.

DNA-binding proteins (DBPs) play a critical role in the development of drugs for treating genetic diseases and in DNA biology research. It is essential for predicting DNA-binding proteins more accurately and efficiently. In this paper, a Laplacian Local Kernel Alignment-based Restricted Kernel Machine (LapLKA-RKM) is proposed to predict DBPs. In detail, we first extract features from the protein sequence using six methods. Second, the Radial Basis Function (RBF) kernel function is utilized to construct pre-defined kernel metrics. Then, these metrics are combined linearly by weights calculated by LapLKA. Finally, the fused kernel is input to RKM for training and prediction. Independent tests and leave-one-out cross-validation were used to validate the performance of our method on a small dataset and two large datasets. Importantly, we built an online platform to represent our model, which is now freely accessible via http://8.130.69.121:8082/.

Characterizing social and cognitive EEG-ERP through multiple kernel learning.

EEG-ERP social-cognitive studies with healthy populations commonly fail to provide significant evidence due to low-quality data and the inherent similarity between groups. We propose a multiple kernel learning-based approach to enhance classification accuracy while keeping the traceability of the features (frequency bands or regions of interest) as a linear combination of kernels. These weights determine the relevance of each source of information, which is crucial for specialists. As a case study, we classify healthy ex-combatants of the Colombian armed conflict and civilians through a cognitive valence recognition task. Although previous works have shown accuracies below 80% with these groups, our proposal achieved an F1 score of 98%, revealing the most relevant bands and brain regions, which are the base for socio-cognitive trainings. With this methodology, we aim to contribute to standardizing EEG analyses and enhancing their statistics.

Identification of drug-side effect association via restricted Boltzmann machines with penalized term.

In the entire life cycle of drug development, the side effect is one of the major failure factors. Severe side effects of drugs that go undetected until the post-marketing stage leads to around two million patient morbidities every year in the United States. Therefore, there is an urgent need for a method to predict side effects of approved drugs and new drugs. Following this need, we present a new predictor for finding side effects of drugs. Firstly, multiple similarity matrices are constructed based on the association profile feature and drug chemical structure information. Secondly, these similarity matrices are integrated by Centered Kernel Alignment-based Multiple Kernel Learning algorithm. Then, Weighted K nearest known neighbors is utilized to complement the adjacency matrix. Next, we construct Restricted Boltzmann machines (RBM) in drug space and side effect space, respectively, and apply a penalized maximum likelihood approach to train model. At last, the average decision rule was adopted to integrate predictions from RBMs. Comparison results and case studies demonstrate, with four benchmark datasets, that our method can give a more accurate and reliable prediction result.

Predict DLBCL patients' recurrence within two years with Gaussian mixture model cluster oversampling and multi-kernel learning.

BACKGROUND AND OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is common in adults' non-Hodgkin's lymphoma. Relapse mainly occurs within two years after diagnosis and has a poor prognosis. Relapse after two years is less frequent and has a better prognosis. In this work, we constructed a relapse prediction model for diffuse large B-cell lymphoma patients within two years, expecting to provide a reference for Clinicians to implement individualized treatment. METHOD: We propose a secondary-level class imbalance method based on Gaussian mixture model (GMM) clustering resampling to balance the data. Then use a multi-kernel support vector machine(SVM) to inscribe heterogeneous clinical data. Finally, merging them to identify recurrence patients within two years. RESULTS: Among all the class imbalance methods in this work, Inverse Weighted -GMM +SMOTEENN has the best performance. Compared with NO-GMM (Directl use the SMOTEENN without the GMM clustering process), its Area Under the ROC Curve(AUC) increases by 8.75%, and ECE and brier scores decrease 2.07% and 3.09%, respectively. Among the four classification algorithms in this work, Multiple kernel learning (MKL) has the most minimized brier scores and expected calibration error(ECE), the largest AUC, accuracy, Recall, precision and F1, has the best discrimination and calibration. CONCLUSION: Our inverse weighted -GMM+SMOTEENN+MKL (GMM-SENN-MKL) method can handle data class imbalance and clinical heterogeneity data well and can be used to predict recurrence in DLBCL patients.

Multi-omics data integration for hepatocellular carcinoma subtyping with multi-kernel learning.

Hepatocellular carcinoma (HCC) is a leading malignant liver tumor with high mortality and morbidity. Patients at the same stage can be defined as different molecular subtypes associated with specific genomic disorders and clinical features. Thus, identifying subtypes is essential to realize efficient treatment and improve survival outcomes of HCC patients. Here, we applied a regularized multiple kernel learning with locality preserving projections method to integrate mRNA, miRNA and DNA methylation data of HCC patients to identify subtypes. We identified two HCC subtypes significantly correlated with the overall survival. The patient 3-years mortality rates in the high-risk and low-risk group was 51.0% and 23.5%, respectively. The high-risk group HCC patients were 3.37 times higher in death risk compared to the low-risk group after adjusting for clinically relevant covariates. A total of 196 differentially expressed mRNAs, 2,151 differentially methylated genes and 58 differentially expressed miRNAs were identified between the two subtypes. Additionally, pathway activity analysis showed that the activities of six pathways between the two subtypes were significantly different. Immune cell infiltration analysis revealed that the abundance of nine immune cells differed significantly between the two subtypes. We further applied the weighted gene co-expression network analysis to identify gene modules that may affect patients prognosis. Among the identified modules, the key module genes significantly associated with prognosis were found to be involved in multiple biological processes and pathways, revealing the mechanism underlying the progression of HCC. Hub gene analysis showed that the expression levels of CDK1, CDCA8, TACC3, and NCAPG were significantly associated with HCC prognosis. Our findings may bring novel insights into the subtypes of HCC and promote the realization of precision medicine.

DRPADC: A novel drug repositioning algorithm predicting adaptive drugs for COVID-19.

Given that the usual process of developing a new vaccine or drug for COVID-19 demands significant time and funds, drug repositioning has emerged as a promising therapeutic strategy. We propose a method named DRPADC to predict novel drug-disease associations effectively from the original sparse drug-disease association adjacency matrix. Specifically, DRPADC processes the original association matrix with the WKNKN algorithm to reduce its sparsity. Furthermore, multiple types of similarity information are fused by a CKA-MKL algorithm. Finally, a compressed sensing algorithm is used to predict the potential drug-disease (virus) association scores. Experimental results show that DRPADC has superior performance than several competitive methods in terms of AUC values and case studies. DRPADC achieved the AUC value of 0.941, 0.955 and 0.876 in Fdataset, Cdataset and HDVD dataset, respectively. In addition, the conducted case studies of COVID-19 show that DRPADC can predict drug candidates accurately.

Altered pattern analysis and identification of subjective cognitive decline based on morphological brain network.

Subjective cognitive decline (SCD) is considered the first stage of Alzheimer's disease (AD). Accurate diagnosis and the exploration of the pathological mechanism of SCD are extremely valuable for targeted AD prevention. However, there is little knowledge of the specific altered morphological network patterns in SCD individuals. In this present study, 36 SCD cases and 34 paired-matched normal controls (NCs) were recruited. The Jensen-Shannon distance-based similarity (JSS) method was implemented to construct and derive the attributes of multiple brain connectomes (i.e., morphological brain connections and global and nodal graph metrics) of individual morphological brain networks. A t-test was used to discriminate between the selected nodal graph metrics, while the leave-one-out cross-validation (LOOCV) was used to obtain consensus connections. Comparisons were performed to explore the altered patterns of connectome features. Further, the multiple kernel support vector machine (MK-SVM) was used for combining brain connectomes and differentiating SCD from NCs. We showed that the consensus connections and nodal graph metrics with the most discriminative ability were mostly found in the frontal, limbic, and parietal lobes, corresponding to the default mode network (DMN) and frontoparietal task control (FTC) network. Altered pattern analysis demonstrated that SCD cases had a tendency for modularity and local efficiency enhancement. Additionally, using the MK-SVM to combine the features of multiple brain connectomes was associated with optimal classification performance [area under the curve (AUC): 0.9510, sensitivity: 97.22%, specificity: 85.29%, and accuracy: 91.43%]. Therefore, our study highlighted the combination of multiple connectome attributes based on morphological brain networks and offered a valuable method for distinguishing SCD individuals from NCs. Moreover, the altered patterns of multidimensional connectome attributes provided a promising insight into the neuroimaging mechanism and early intervention in SCD subjects.

Machine Learning Techniques for the Diagnosis of Schizophrenia Based on Event-Related Potentials.

Antecedent: The event-related potential (ERP) components P300 and mismatch negativity (MMN) have been linked to cognitive deficits in patients with schizophrenia. The diagnosis of schizophrenia could be improved by applying machine learning procedures to these objective neurophysiological biomarkers. Several studies have attempted to achieve this goal, but no study has examined Multiple Kernel Learning (MKL) classifiers. This algorithm finds optimally a combination of kernel functions, integrating them in a meaningful manner, and thus could improve diagnosis. Objective: This study aimed to examine the efficacy of the MKL classifier and the Boruta feature selection method for schizophrenia patients (SZ) and healthy controls (HC) single-subject classification. Methods: A cohort of 54 SZ and 54 HC participants were studied. Three sets of features related to ERP signals were calculated as follows: peak related features, peak to peak related features, and signal related features. The Boruta algorithm was used to evaluate the impact of feature selection on classification performance. An MKL algorithm was applied to address schizophrenia detection. Results: A classification accuracy of 83% using the whole dataset, and 86% after applying Boruta feature selection was obtained. The variables that contributed most to the classification were mainly related to the latency and amplitude of the auditory P300 paradigm. Conclusion: This study showed that MKL can be useful in distinguishing between schizophrenic patients and controls when using ERP measures. Moreover, the use of the Boruta algorithm provides an improvement in classification accuracy and computational cost.

Prediction of high and low disease activity in early MS patients using multiple kernel learning identifies importance of lateral ventricle intensity.

Background: Lack of easy-to-interpret disease activity prediction methods in early MS can lead to worse patient prognosis. Objectives: Using machine learning (multiple kernel learning - MKL) models, we assessed the prognostic value of various clinical and MRI measures for disease activity. Methods: Early MS patients (n = 148) with at least two associated clinical and MRI visits were investigated. T2-weighted MRIs were cropped to contain mainly the lateral ventricles (LV). High disease activity was defined as surpassing NEDA-3 Criteria more than once per year. Clinical demographic, MRI-extracted image-derived phenotypes (IDP), and MRI data were used as inputs for separate kernels to predict future disease activity with MKL. Model performance was compared using bootstrapped effect size analysis of mean differences. Results: A total of 681 visits were included, where 81 (55%) patients had high disease activity in a combined end point measure using all follow-up visits. MKL model discrimination performance was moderate (AUC ≥ 0.62); however, modelling with combined clinical and cropped LV kernels gave the highest prediction performance (AUC = 0.70). Conclusions: MRIs contain valuable information on future disease activity, especially in and around the LV. MKL techniques for combining different data types can be used for the prediction of disease activity in a relatively small MS cohort.

Structural Features Predict Sexual Trauma and Interpersonal Problems in Borderline Personality Disorder but Not in Controls: A Multi-Voxel Pattern Analysis.

Child trauma plays an important role in the etiology of Bordeline Personality Disorder (BPD). Of all traumas, sexual trauma is the most common, severe and most associated with receiving a BPD diagnosis when adult. Etiologic models posit sexual abuse as a prognostic factor in BPD. Here we apply machine learning using Multiple Kernel Regression to the Magnetic Resonance Structural Images of 20 BPD and 13 healthy control (HC) to see whether their brain predicts five sources of traumas: sex abuse, emotion neglect, emotional abuse, physical neglect, physical abuse (Child Trauma Questionnaire; CTQ). We also applied the same analysis to predict symptom severity in five domains: affective, cognitive, impulsivity, interpersonal (Zanarini Rating Scale for Borderline Personality Disorder; Zan-BPD) for BPD patients only. Results indicate that CTQ sexual trauma is predicted by a set of areas including the amygdala, the Heschl area, the Caudate, the Putamen, and portions of the Cerebellum in BPD patients only. Importantly, interpersonal problems only in BPD patients were predicted by a set of areas including temporal lobe and cerebellar regions. Notably, sexual trauma and interpersonal problems were not predicted by structural features in matched healthy controls. This finding may help elucidate the brain circuit affected by traumatic experiences and connected with interpersonal problems BPD suffer from.

HKAM-MKM: A hybrid kernel alignment maximization-based multiple kernel model for identifying DNA-binding proteins.

The identification of DNA-binding proteins (DBPs) has always been a hot issue in the field of sequence classification. However, considering that the experimental identification method is very resource-intensive, the construction of a computational prediction model is worthwhile. This study developed and evaluated a hybrid kernel alignment maximization-based multiple kernel model (HKAM-MKM) for predicting DBPs. First, we collected two datasets and performed feature extraction on the sequences to obtain six feature groups, and then constructed the corresponding kernels. To ensure the effective utilisation of the base kernel and avoid ignoring the difference between the sample and its neighbours, we proposed local kernel alignment to calculate the kernel between the sample and its neighbours, with each sample as the centre. We combined the global and local kernel alignments to develop a hybrid kernel alignment model, and balance the relationship between the two through parameters. By maximising the hybrid kernel alignment value, we obtained the weight of each kernel and then linearly combined the kernels in the form of weights. Finally, the fused kernel was input into a support vector machine for training and prediction. Finally, in the independent test sets PDB186 and PDB2272, we obtained the highest Matthew's correlation coefficient (MCC) (0.768 and 0.5962, respectively) and the highest accuracy (87.1% and 78.43%, respectively), which were superior to the other predictors. Therefore, HKAM-MKM is an efficient prediction tool for DBPs.

Identification of drug-target interactions via multiple kernel-based triple collaborative matrix factorization.

Targeted drugs have been applied to the treatment of cancer on a large scale, and some patients have certain therapeutic effects. It is a time-consuming task to detect drug-target interactions (DTIs) through biochemical experiments. At present, machine learning (ML) has been widely applied in large-scale drug screening. However, there are few methods for multiple information fusion. We propose a multiple kernel-based triple collaborative matrix factorization (MK-TCMF) method to predict DTIs. The multiple kernel matrices (contain chemical, biological and clinical information) are integrated via multi-kernel learning (MKL) algorithm. And the original adjacency matrix of DTIs could be decomposed into three matrices, including the latent feature matrix of the drug space, latent feature matrix of the target space and the bi-projection matrix (used to join the two feature spaces). To obtain better prediction performance, MKL algorithm can regulate the weight of each kernel matrix according to the prediction error. The weights of drug side-effects and target sequence are the highest. Compared with other computational methods, our model has better performance on four test data sets.

Multiple domain and multiple kernel outcome-weighted learning for estimating individualized treatment regimes.

Individualized treatment rules (ITRs) recommend treatments that are tailored specifically according to each patient's own characteristics. It can be challenging to estimate optimal ITRs when there are many features, especially when these features have arisen from multiple data domains (e.g., demographics, clinical measurements, neuroimaging modalities). Considering data from complementary domains and using multiple similarity measures to capture the potential complex relationship between features and treatment can potentially improve the accuracy of assigning treatments. Outcome weighted learning (OWL) methods that are based on support vector machines using a predetermined single kernel function have previously been developed to estimate optimal ITRs. In this paper, we propose an approach to estimate optimal ITRs by exploiting multiple kernel functions to describe the similarity of features between subjects both within and across data domains within the OWL framework, as opposed to preselecting a single kernel function to be used for all features for all domains. Our method takes into account the heterogeneity of each data domain and combines multiple data domains optimally. Our learning process estimates optimal ITRs and also identifies the data domains that are most important for determining ITRs. This approach can thus be used to prioritize the collection of data from multiple domains, potentially reducing cost without sacrificing accuracy. The comparative advantage of our method is demonstrated by simulation studies and by an application to a randomized clinical trial for major depressive disorder that collected features from multiple data domains. Supplemental materials for this article are available online.

PrognosiT: Pathway/gene set-based tumour volume prediction using multiple kernel learning.

BACKGROUND: Identification of molecular mechanisms that determine tumour progression in cancer patients is a prerequisite for developing new disease treatment guidelines. Even though the predictive performance of current machine learning models is promising, extracting significant and meaningful knowledge from the data simultaneously during the learning process is a difficult task considering the high-dimensional and highly correlated nature of genomic datasets. Thus, there is a need for models that not only predict tumour volume from gene expression data of patients but also use prior information coming from pathway/gene sets during the learning process, to distinguish molecular mechanisms which play crucial role in tumour progression and therefore, disease prognosis. RESULTS: In this study, instead of initially choosing several pathways/gene sets from an available set and training a model on this previously chosen subset of genomic features, we built a novel machine learning algorithm, PrognosiT, that accomplishes both tasks together. We tested our algorithm on thyroid carcinoma patients using gene expression profiles and cancer-specific pathways/gene sets. Predictive performance of our novel multiple kernel learning algorithm (PrognosiT) was comparable or even better than random forest (RF) and support vector regression (SVR). It is also notable that, to predict tumour volume, PrognosiT used gene expression features less than one-tenth of what RF and SVR algorithms used. CONCLUSIONS: PrognosiT was able to obtain comparable or even better predictive performance than SVR and RF. Moreover, we demonstrated that during the learning process, our algorithm managed to extract relevant and meaningful pathway/gene sets information related to the studied cancer type, which provides insights about its progression and aggressiveness. We also compared gene expressions of the selected genes by our algorithm in tumour and normal tissues, and we then discussed up- and down-regulated genes selected by our algorithm while learning, which could be beneficial for determining new biomarkers.

Multimodal MR Images-Based Diagnosis of Early Adolescent Attention-Deficit/Hyperactivity Disorder Using Multiple Kernel Learning.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common brain diseases among children. The current criteria of ADHD diagnosis mainly depend on behavior analysis, which is subjective and inconsistent, especially for children. The development of neuroimaging technologies, such as magnetic resonance imaging (MRI), drives the discovery of brain abnormalities in structure and function by analyzing multimodal neuroimages for computer-aided diagnosis of brain diseases. This paper proposes a multimodal machine learning framework that combines the Boruta based feature selection and Multiple Kernel Learning (MKL) to integrate the multimodal features of structural and functional MRIs and Diffusion Tensor Images (DTI) for the diagnosis of early adolescent ADHD. The rich and complementary information of the macrostructural features, microstructural properties, and functional connectivities are integrated at the kernel level, followed by a support vector machine classifier for discriminating ADHD from healthy children. Our experiments were conducted on the comorbidity-free ADHD subjects and covariable-matched healthy children aged 9-10 chosen from the Adolescent Brain and Cognitive Development (ABCD) study. This paper is the first work to combine structural and functional MRIs with DTI for early adolescents of the ABCD study. The results indicate that the kernel-level fusion of multimodal features achieves 0.698 of AUC (area under the receiver operating characteristic curves) and 64.3% of classification accuracy for ADHD diagnosis, showing a significant improvement over the early feature fusion and unimodal features. The abnormal functional connectivity predictors, involving default mode network, attention network, auditory network, and sensorimotor mouth network, thalamus, and cerebellum, as well as the anatomical regions in basal ganglia, are found to encode the most discriminative information, which collaborates with macrostructure and diffusion alterations to boost the performances of disorder diagnosis.

A review on machine learning approaches and trends in drug discovery.

Drug discovery aims at finding new compounds with specific chemical properties for the treatment of diseases. In the last years, the approach used in this search presents an important component in computer science with the skyrocketing of machine learning techniques due to its democratization. With the objectives set by the Precision Medicine initiative and the new challenges generated, it is necessary to establish robust, standard and reproducible computational methodologies to achieve the objectives set. Currently, predictive models based on Machine Learning have gained great importance in the step prior to preclinical studies. This stage manages to drastically reduce costs and research times in the discovery of new drugs. This review article focuses on how these new methodologies are being used in recent years of research. Analyzing the state of the art in this field will give us an idea of where cheminformatics will be developed in the short term, the limitations it presents and the positive results it has achieved. This review will focus mainly on the methods used to model the molecular data, as well as the biological problems addressed and the Machine Learning algorithms used for drug discovery in recent years.

Identifying resting state differences salient for resilience to chronic pain based on machine learning multivariate pattern analysis.

Studies have documented behavior differences between more versus less resilient adults with chronic pain (CP), but the presence and nature of underlying neurophysiological differences have received scant attention. In this study, we attempted to identify regions of interest (ROIs) in which resting state (Rs) brain activity discriminated more from less resilient CP subgroups based on multiple kernel learning (MKL). More and less resilient community-dwellers with chronic musculoskeletal pain (70 women, 39 men) engaged in structural and functional magnetic resonance imaging (MRI) scans, wherein MKL assessed Rs activity based on amplitude of low frequency fluctuations (ALFF), fractional amplitudes of low frequency fluctuations (fALFF), and regional homogeneity (ReHo) modalities to identify ROIs most salient for discriminating more versus less resilient subgroups. Compared to classification based on single modalities, multi-modal classification based on combined fALFF and ReHo features achieved a substantially higher classification accuracy rate (79%). Brain regions with the best discriminative power included those implicated in pain processing, reward, executive function, goal-directed action, emotion regulation and resilience to mood disorders though variation trends were not consistent between more and less resilient subgroups. Results revealed patterns of Rs activity that serve as possible biomarkers for resilience to chronic musculoskeletal pain.