Meta-learning-based Inductive logistic matrix completion for prediction of kinase inhibitors.

Protein kinases become an important source of potential drug targets. Developing new, efficient, and safe small-molecule kinase inhibitors has become an important topic in the field of drug research and development. In contrast with traditional wet experiments which are time-consuming and expensive, machine learning-based approaches for predicting small molecule inhibitors for protein kinases are time-saving and cost-effective, which are highly desired for us. However, the issue of sample scarcity (known active and inactive compounds are usually limited for most kinases) poses a challenge to the research and development of machine learning-based kinase inhibitors' active prediction methods. To alleviate the data scarcity problem in the prediction of kinase inhibitors, in this study, we present a novel Meta-learning-based inductive logistic matrix completion method for the Prediction of Kinase Inhibitors (MetaILMC). MetaILMC adopts a meta-learning framework to learn a well-generalized model from tasks with sufficient samples, which can fast adapt to new tasks with limited samples. As MetaILMC allows the effective transfer of the prior knowledge learned from kinases with sufficient samples to kinases with a small number of samples, the proposed model can produce accurate predictions for kinases with limited data. Experimental results show that MetaILMC has excellent performance for prediction tasks of kinases with few-shot samples and is significantly superior to the state-of-the-art multi-task learning in terms of AUC, AUPR, etc., various performance metrics. Case studies also provided for two drugs to predict Kinase Inhibitory scores, further validating the proposed method's effectiveness and feasibility. SCIENTIFIC CONTRIBUTION: Considering the potential correlation between activity prediction tasks for different kinases, we propose a novel meta learning algorithm MetaILMC, which learns a prior of strong generalization capacity during meta-training from the tasks with sufficient training samples, such that it can be easily and quickly adapted to the new tasks of the kinase with scarce data during meta-testing. Thus, MetaILMC can effectively alleviate the data scarcity problem in the prediction of kinase inhibitors.

MT-EpiPred: Multitask Learning for Prediction of Small-Molecule Epigenetic Modulators.

Epigenetic modulators play an increasingly crucial role in the treatment of various diseases. In this case, it is imperative to systematically investigate the activity of these agents and understand their influence on the entire epigenetic regulatory network rather than solely concentrate on individual targets. This work introduces MT-EpiPred, a multitask learning method capable of predicting the activity of compounds against 78 epigenetic targets. MT-EpiPred demonstrated outstanding performance, boasting an average auROC of 0.915 and the ability to handle few-shot targets. In comparison to the existing method, MT-EpiPred not only expands the target pool but also achieves superior predictive performance with the same data set. MT-EpiPred was then applied to predict the epigenetic target of a newly synthesized compound (1), where the molecular target was unknown. The method identified KDM4D as a potential target, which was subsequently validated through an in vitro enzyme inhibition assay, revealing an IC50 of 4.8 µM. The MT-EpiPred method has been implemented in the web server MT-EpiPred (http://epipred.com), providing free accessibility. In summary, this work presents a convenient and accurate tool for discovering novel small-molecule epigenetic modulators, particularly in the development of selective inhibitors and evaluating the impact of these inhibitors over a broad epigenetic network.

A deep learning model using hyperspectral image for EUS-FNA cytology diagnosis in pancreatic ductal adenocarcinoma.

BACKGROUND AND AIMS: Endoscopic ultrasonography-guided fine-needle aspiration/biopsy (EUS-FNA/B) is considered to be a first-line procedure for the pathological diagnosis of pancreatic cancer owing to its high accuracy and low complication rate. The number of new cases of pancreatic ductal adenocarcinoma (PDAC) is increasing, and its accurate pathological diagnosis poses a challenge for cytopathologists. Our aim was to develop a hyperspectral imaging (HSI)-based convolution neural network (CNN) algorithm to aid in the diagnosis of pancreatic EUS-FNA cytology specimens. METHODS: HSI images were captured of pancreatic EUS-FNA cytological specimens from benign pancreatic tissues (n = 33) and PDAC (n = 39) prepared using a liquid-based cytology method. A CNN was established to test the diagnostic performance, and Attribution Guided Factorization Visualization (AGF-Visualization) was used to visualize the regions of important classification features identified by the model. RESULTS: A total of 1913 HSI images were obtained. Our ResNet18-SimSiam model achieved an accuracy of 0.9204, sensitivity of 0.9310 and specificity of 0.9123 (area under the curve of 0.9625) when trained on HSI images for the differentiation of PDAC cytological specimens from benign pancreatic cells. AGF-Visualization confirmed that the diagnoses were based on the features of tumor cell nuclei. CONCLUSIONS: An HSI-based model was developed to diagnose cytological PDAC specimens obtained using EUS-guided sampling. Under the supervision of experienced cytopathologists, we performed multi-staged consecutive in-depth learning of the model. Its superior diagnostic performance could be of value for cytologists when diagnosing PDAC.