Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Automated brain hematoma segmentation and outcome prediction for patients with TBI can effectively facilitate patient management. In this study, we propose a novel Multi-view convolutional neural network with a mixed loss to segment total acute hematoma on head CT scans collected within 24 h after the injury. Based on the automated segmentation, the volumetric distribution and shape characteristics of the hematoma were extracted and combined with other clinical observations to predict 6-month mortality. The proposed hematoma segmentation network achieved an average Dice coefficient of 0.697 and an intraclass correlation coefficient of 0.966 between the volumes estimated from the predicted hematoma segmentation and volumes of the annotated hematoma segmentation on the test set. Compared with other published methods, the proposed method has the most accurate segmentation performance and volume estimation. For 6-month mortality prediction, the model achieved an average area under the precision-recall curve (AUCPR) of 0.559 and area under the receiver operating characteristic curve (AUC) of 0.853 using 10-fold cross-validation on a dataset consisting of 828 patients. The average AUCPR and AUC of the proposed model are respectively more than 10% and 5% higher than those of the widely used IMPACT model.

Optical colonoscopy is an essential diagnostic and prognostic tool for many gastrointestinal diseases, including cancer screening and staging, intestinal bleeding, diarrhea, abdominal symptom evaluation, and inflammatory bowel disease assessment. However, the evaluation, classification, and quantification of findings from colonoscopy are subject to inter-observer variation. Automated assessment of colonoscopy is of interest considering the subjectivity present in qualitative human interpretations of colonoscopy findings. Localization of the camera is essential to interpreting the meaning and context of findings for diseases evaluated by colonoscopy. In this study, we propose a camera localization system to estimate the relative location of the camera and classify the colon into anatomical segments. The camera localization system begins with non-informative frame detection and removal. Then a self-training end-to-end convolutional neural network is built to estimate the camera motion, where several strategies are proposed to improve its robustness and generalization on endoscopic videos. Using the estimated camera motion a camera trajectory can be derived and a relative location index calculated. Based on the estimated location index, anatomical colon segment classification is performed by constructing a colon template. The proposed motion estimation algorithm was evaluated on an external dataset containing the ground truth for camera pose. The experimental results show that the performance of the proposed method is superior to other published methods. The relative location index estimation and anatomical region classification were further validated using colonoscopy videos collected from routine clinical practice. This validation yielded an average accuracy in classification of 0.754, which is substantially higher than the performances obtained using location indices built from other methods.

A model's interpretability is essential to many practical applications such as clinical decision support systems. In this paper, a novel interpretable machine learning method is presented, which can model the relationship between input variables and responses in humanly understandable rules. The method is built by applying tropical geometry to fuzzy inference systems, wherein variable encoding functions and salient rules can be discovered by supervised learning. Experiments using synthetic datasets were conducted to demonstrate the performance and capacity of the proposed algorithm in classification and rule discovery. Furthermore, we present a pilot application in identifying heart failure patients that are eligible for advanced therapies as proof of principle. From our results on this particular application, the proposed network achieves the highest F1 score. The network is capable of learning rules that can be interpreted and used by clinical providers. In addition, existing fuzzy domain knowledge can be easily transferred into the network and facilitate model training. In our application, with the existing knowledge, the F1 score was improved by over 5%. The characteristics of the proposed network make it promising in applications requiring model reliability and justification.

Reversible posttranslational modification (PTM) plays a very important role in biological process by changing properties of proteins. As many proteins are multiply modified by PTMs, cross talk of PTMs is becoming an intriguing topic and draws much attention. Currently, lots of evidences suggest that the PTMs work together to accomplish a specific biological function. However, both the general principles and underlying mechanism of PTM crosstalk are elusive. In this study, by using large-scale datasets we performed evolutionary conservation analysis, gene ontology enrichment, motif extraction of proteins with cross talk of O-GlcNAcylation and phosphorylation cooccurring on the same residue. We found that proteins within situO-GlcNAc/Phos cross talk were significantly enriched in some specific gene ontology terms and no obvious evolutionary pressure was observed. Moreover, 3 functional motifs associated with O-GlcNAc/Phos sites were extracted. We further used sequence features and GO features to predict O-GlcNAc/Phos cross talk sites based on phosphorylated sites and O-GlcNAcylated sites separately by the use of SVM model. The AUC of classifier based on phosphorylated sites is 0.896 and the other classifier based on GlcNAcylated sites is 0.843. Both classifiers achieved a relatively better performance compared with other existing methods.

Systems level barriers to heart failure (HF) care limit access to HF advanced therapies (heart transplantation, left ventricular assist devices). There is a need for automated systems that can help clinicians ensure patients with HF are evaluated for HF advanced therapies at the appropriate time to optimize outcomes. We performed a retrospective study using the REVIVAL (Registry Evaluation of Vital Information for VADs in Ambulatory Life) and INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registries. We developed a novel machine learning model based on principles of tropical geometry and fuzzy logic that can accommodate clinician knowledge and provide recommendations regarding need for advanced therapies evaluations that are accessible to end-users. The model was trained and validated using data from 4,694 HF patients. When initiated with clinical knowledge from HF and transplant cardiologists, the model achieved an F1 score of 43.8%, recall of 51.1%, and precision of 46.9%. The model achieved comparable performance compared with other commonly used machine learning models. Importantly, our model was 1 of only 3 models providing transparent and parsimonious clinical rules, significantly outperforming the other 2 models. Eleven clinical rules were extracted from the model which can be leveraged in clinical practice. A machine learning model capable of accepting clinical knowledge and making accessible recommendations was trained to identify patients with advanced HF. While this model was developed for HF care, the methodology has multiple potential uses in other important clinical applications.

Phenotypic drug discovery has yielded many first-in-class small-molecule drugs by discovering modulators of disease phenotypes in physiologically relevant cellular systems. However, high-content phenotypic assays lack the ultra-high-throughput scalability of target-based screens. Recent advances in virtual screening present an opportunity to address this bottleneck, but have been limited to simple phenotypes like viability, restricted to small repurposing libraries, or lack in-depth biological validation. Here, we present PhenoCompass, a multimodal co-embedding model that aligns compound structures and high-content phenotypic imaging to enable virtual phenotypic screening over billion-compound libraries. Following training on the Joint Undertaking in Morphology dataset with more than 100,000 Cell Painting compound profiles, retrospective validation with historical biochemical high-throughput screening data demonstrates that PhenoCompass ranks compounds according to their biochemical target engagement. Leveraging PhenoCompass, we performed a prospective screen of 3.8 billion Enamine REAL compounds for inhibitors of PI3K/mTOR pathway, a critical signaling cascade whose aberrant activation is a common tumor driver. This search identified 11 novel compounds with pathway-consistent Cell Painting readout and diverse scaffolds, a 54-fold enrichment over the training set. Orthogonal validation experiments using a FOXO3A reporter assay and direct kinase inhibition confirmed seven structurally novel inhibitors with distinct mechanisms of action. These results highlight the convergence of diverse molecular target profiles onto a shared morphological pathway signature and establish PhenoCompass as a robust framework for high-content phenotypic virtual screening.