Artificial intelligence (AI) has been widely applied in drug discovery with a major task as molecular property prediction. Despite booming techniques in molecular representation learning, key elements underlying molecular property prediction remain largely unexplored, which impedes further advancements in this field. Herein, we conduct an extensive evaluation of representative models using various representations on the MoleculeNet datasets, a suite of opioids-related datasets and two additional activity datasets from the literature. To investigate the predictive power in low-data and high-data space, a series of descriptors datasets of varying sizes are also assembled to evaluate the models. In total, we have trained 62,820 models, including 50,220 models on fixed representations, 4200 models on SMILES sequences and 8400 models on molecular graphs. Based on extensive experimentation and rigorous comparison, we show that representation learning models exhibit limited performance in molecular property prediction in most datasets. Besides, multiple key elements underlying molecular property prediction can affect the evaluation results. Furthermore, we show that activity cliffs can significantly impact model prediction. Finally, we explore into potential causes why representation learning models can fail and show that dataset size is essential for representation learning models to excel.

Background: With increased specialization of health care services and high levels of patient mobility, accessing health care services across multiple hospitals or clinics has become very common for diagnosis and treatment, particularly for patients with chronic diseases such as cancer. With informed knowledge of a patient’s history, physicians can make prompt clinical decisions for smarter, safer, and more efficient care. However, due to the privacy and high sensitivity of electronic health records (EHR), most EHR data sharing still happens through fax or mail due to the lack of systematic infrastructure support for secure, trustable health data sharing, which can also cause major delays in patient care. Objective: Our goal was to develop a system that will facilitate secure, trustable management, sharing, and aggregation of EHR data. Our patient-centric system allows patients to manage their own health records across multiple hospitals. The system will ensure patient privacy protection and guarantee security with respect to the requirements for health care data management, including the access control policy specified by the patient. Methods: We propose a permissioned blockchain-based system for EHR data sharing and integration. Each hospital will provide a blockchain node integrated with its own EHR system to form the blockchain network. A web-based interface will be used for patients and doctors to initiate EHR sharing transactions. We take a hybrid data management approach, where only management metadata will be stored on the chain. Actual EHR data, on the other hand, will be encrypted and stored off-chain in Health Insurance Portability and Accountability Act–compliant cloud-based storage. The system uses public key infrastructure–based asymmetric encryption and digital signatures to secure shared EHR data. Results: In collaboration with Stony Brook University Hospital, we developed ACTION-EHR, a system for patient-centric, blockchain-based EHR data sharing and management for patient care, in particular radiation treatment for cancer. The prototype was built on Hyperledger Fabric, an open-source, permissioned blockchain framework. Data sharing transactions were implemented using chaincode and exposed as representational state transfer application programming interfaces used for the web portal for patients and users. The HL7 Fast Healthcare Interoperability Resources standard was adopted to represent shared EHR data, making it easy to interface with hospital EHR systems and integrate a patient’s EHR data. We tested the system in a distributed environment at Stony Brook University using deidentified patient data. Conclusions: We studied and developed the critical technology components to enable patient-centric, blockchain-based EHR sharing to support cancer care. The prototype demonstrated the feasibility of our approach as well as some of the major challenges. The next step will be a pilot study with health care providers in both the United States and Switzerland. Our work provides an exemplar testbed to build next-generation EHR sharing infrastructures.

Background: In recent years, both suicide and overdose rates have been increasing. Many individuals who struggle with opioid use disorder are prone to suicidal ideation; this may often result in overdose. However, these fatal overdoses are difficult to classify as intentional or unintentional. Intentional overdose is difficult to detect, partially due to the lack of predictors and social stigmas that push individuals away from seeking help. These individuals may instead use web-based means to articulate their concerns. Objective: This study aimed to extract posts of suicidality among opioid users on Reddit using machine learning methods. The performance of the models is derivative of the data purity, and the results will help us to better understand the rationale of these users, providing new insights into individuals who are part of the opioid epidemic. Methods: Reddit posts between June 2017 and June 2018 were collected from r/suicidewatch, r/depression, a set of opioid-related subreddits, and a control subreddit set. We first classified suicidal versus nonsuicidal languages and then classified users with opioid usage versus those without opioid usage. Several traditional baselines and neural network (NN) text classifiers were trained using subreddit names as the labels and combinations of semantic inputs. We then attempted to extract out-of-sample data belonging to the intersection of suicide ideation and opioid abuse. Amazon Mechanical Turk was used to provide labels for the out-of-sample data. Results: Classification results were at least 90% across all models for at least one combination of input; the best classifier was convolutional neural network, which obtained an F1 score of 96.6%. When predicting out-of-sample data for posts containing both suicidal ideation and signs of opioid addiction, NN classifiers produced more false positives and traditional methods produced more false negatives, which is less desirable for predicting suicidal sentiments. Conclusions: Opioid abuse is linked to the risk of unintentional overdose and suicide risk. Social media platforms such as Reddit contain metadata that can aid machine learning and provide information at a personal level that cannot be obtained elsewhere. We demonstrate that it is possible to use NNs as a tool to predict an out-of-sample target with a model built from data sets labeled by characteristics we wish to distinguish in the out-of-sample target.

Predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) patients accurately is direly needed for clinical decision making. pCR is also regarded as a strong predictor of overall survival. In this work, we propose a deep learning system to predict pCR to NAC based on serial pathology images stained with hematoxylin and eosin and two immunohistochemical biomarkers (Ki67 and PHH3). To support human prior domain knowledge-based guidance and enhance interpretability of the deep learning system, we introduce a human knowledge-derived spatial attention mechanism to inform deep learning models of informative tissue areas of interest. For each patient, three serial breast tumor tissue sections from biopsy blocks were sectioned, stained in three different stains and integrated. The resulting comprehensive attention information from the image triplets is used to guide our prediction system for prognostic tissue regions. The experimental dataset consists of 26 419 pathology image patches of $1000×1000$ pixels from 73 TNBC patients treated with NAC. Image patches from randomly selected 43 patients are used as a training dataset and images patches from the rest 30 are used as a testing dataset. By the maximum voting from patch-level results, our proposed model achieves a 93% patient-level accuracy, outperforming baselines and other state-of-the-art systems, suggesting its high potential for clinical decision making. The codes, the documentation and example data are available on an open source at: https://github.com/jkonglab/PCR_Prediction_Serial_WSIs_biomarkers Supplementary data are available at Bioinformatics online.