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Register a new userA Random Interaction Forest for Prioritizing Predictive Biomarkers
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Precision medicine is becoming a focus in medical research recently, as its implementation brings values to all stakeholders in the healthcare system. Various statistical methodologies have been developed tackling problems in different aspects of this field, e.g., assessing treatment heterogeneity, identifying patient subgroups, or building treatment decision models. However, there is a lack of new tools devoted to selecting and prioritizing predictive biomarkers. We propose a novel tree-based ensemble method, random interaction forest (RIF), to generate predictive importance scores and prioritize candidate biomarkers for constructing refined treatment decision models. RIF was evaluated by comparing with the conventional random forest and univariable regression methods and showed favorable properties under various simulation scenarios. We applied the proposed RIF method to a biomarker dataset from two phase III clinical trials of bezlotoxumab on $textit{Clostridium difficile}$ infection recurrence and obtained biologically meaningful results.
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We propose a hybrid sequential deep learning model to predict the risk of AMD progression in non-exudative AMD eyes at multiple timepoints, starting from short-term progression (3-months) up to long-term progression (21-months). Proposed model combines radiomics and deep learning to handle challenges related to imperfect ratio of OCT scan dimension and training cohort size. We considered a retrospective clinical trial dataset that includes 671 fellow eyes with 13,954 dry AMD observations for training and validating the machine learning models on a 10-fold cross validation setting. The proposed RNN model achieved high accuracy (0.96 AUCROC) for the prediction of both short term and long-term AMD progression, and outperformed the traditional random forest model trained. High accuracy achieved by the RNN establishes the ability to identify AMD patients at risk of progressing to advanced AMD at an early stage which could have a high clinical impact as it allows for optimal clinical follow-up, with more frequent screening and potential earlier treatment for those patients at high risk.
The aim of the systematic review was to assess recently published studies on diagnostic test accuracy of glioblastoma treatment response monitoring biomarkers in adults, developed through machine learning (ML). Articles were searched for using MEDLINE, EMBASE, and the Cochrane Register. Included study participants were adult patients with high grade glioma who had undergone standard treatment (maximal resection, radiotherapy with concomitant and adjuvant temozolomide) and subsequently underwent follow-up imaging to determine treatment response status. Risk of bias and applicability was assessed with QUADAS 2 methodology. Contingency tables were created for hold-out test sets and recall, specificity, precision, F1-score, balanced accuracy calculated. Fifteen studies were included with 1038 patients in training sets and 233 in test sets. To determine whether there was progression or a mimic, the reference standard combination of follow-up imaging and histopathology at re-operation was applied in 67% of studies. The small numbers of patient included in studies, the high risk of bias and concerns of applicability in the study designs (particularly in relation to the reference standard and patient selection due to confounding), and the low level of evidence, suggest that limited conclusions can be drawn from the data. There is likely good diagnostic performance of machine learning models that use MRI features to distinguish between progression and mimics. The diagnostic performance of ML using implicit features did not appear to be superior to ML using explicit features. There are a range of ML-based solutions poised to become treatment response monitoring biomarkers for glioblastoma. To achieve this, the development and validation of ML models require large, well-annotated datasets where the potential for confounding in the study design has been carefully considered.
Three major biomarkers: beta-amyloid (A), pathologic tau (T), and neurodegeneration (N), are recognized as valid proxies for neuropathologic changes of Alzheimers disease. While there are extensive studies on cerebrospinal fluids biomarkers (amyloid, tau), the spatial propagation pattern across brain is missing and their interactive mechanisms with neurodegeneration are still unclear. To this end, we aim to analyze the spatiotemporal associations between ATN biomarkers using large-scale neuroimaging data. We first investigate the temporal appearances of amyloid plaques, tau tangles, and neuronal loss by modeling the longitudinal transition trajectories. Second, we propose linear mixed-effects models to quantify the pathological interactions and propagation of ATN biomarkers at each brain region. Our analysis of the current data shows that there exists a temporal latency in the build-up of amyloid to the onset of tau pathology and neurodegeneration. The propagation pattern of amyloid can be characterized by its diffusion along the topological brain network. Our models provide sufficient evidence that the progression of pathological tau and neurodegeneration share a strong regional association, which is different from amyloid.
Prediction of Overall Survival (OS) of brain cancer patients from multi-modal MRI is a challenging field of research. Most of the existing literature on survival prediction is based on Radiomic features, which does not consider either non-biological factors or the functional neurological status of the patient(s). Besides, the selection of an appropriate cut-off for survival and the presence of censored data create further problems. Application of deep learning models for OS prediction is also limited due to the lack of large annotated publicly available datasets. In this scenario we analyse the potential of two novel neuroimaging feature families, extracted from brain parcellation atlases and spatial habitats, along with classical radiomic and geometric features; to study their combined predictive power for analysing overall survival. A cross validation strategy with grid search is proposed to simultaneously select and evaluate the most predictive feature subset based on its predictive power. A Cox Proportional Hazard (CoxPH) model is employed for univariate feature selection, followed by the prediction of patient-specific survival functions by three multivariate parsimonious models viz. Coxnet, Random survival forests (RSF) and Survival SVM (SSVM). The brain cancer MRI data used for this research was taken from two open-access collections TCGA-GBM and TCGA-LGG available from The Cancer Imaging Archive (TCIA). Corresponding survival data for each patient was downloaded from The Cancer Genome Atlas (TCGA). A high cross validation $C-index$ score of $0.82pm.10$ was achieved using RSF with the best $24$ selected features. Age was found to be the most important biological predictor. There were $9$, $6$, $6$ and $2$ features selected from the parcellation, habitat, radiomic and region-based feature groups respectively.
The novel coronavirus disease, named COVID-19, emerged in China in December 2019, and has rapidly spread around the world. It is clearly urgent to fight COVID-19 at global scale. The development of methods for identifying drug uses based on phenotypic data can improve the efficiency of drug development. However, there are still many difficulties in identifying drug applications based on cell picture data. This work reported one state-of-the-art machine learning method to identify drug uses based on the cell image features of 1024 drugs generated in the LINCS program. Because the multi-dimensional features of the image are affected by non-experimental factors, the characteristics of similar drugs vary greatly, and the current sample number is not enough to use deep learning and other methods are used for learning optimization. As a consequence, this study is based on the supervised ITML algorithm to convert the characteristics of drugs. The results show that the characteristics of ITML conversion are more conducive to the recognition of drug functions. The analysis of feature conversion shows that different features play important roles in identifying different drug functions. For the current COVID-19, Chloroquine and Hydroxychloroquine achieve antiviral effects by inhibiting endocytosis, etc., and were classified to the same community. And Clomiphene in the same community inibited the entry of Ebola Virus, indicated a similar MoAs that could be reflected by cell image.
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