scholarly journals MatchMaker: A Deep Learning Framework for Drug Synergy Prediction

2020 ◽  
Author(s):  
Halil Ibrahim Kuru ◽  
Oznur Tastan ◽  
A. Ercument Cicek
Keyword(s):  
Deep Learning ◽  
Drug Combination ◽  
Mean Squared Error ◽  
Expression Profiles ◽  
Search Space ◽  
Computational Techniques ◽  
Combinatorial Search ◽  
Structure Information ◽  
Drug Synergy ◽  
Learning Framework

AbstractDrug combination therapies have been a viable strategy for the treatment of complex diseases such as cancer due to increased efficacy and reduced side effects. However, experimentally validating all possible combinations for synergistic interaction even with high-throughout screens is intractable due to vast combinatorial search space. Computational techniques can reduce the number of combinations to be evaluated experimentally by prioritizing promising candidates. We present MatchMaker that predicts drug synergy scores using drug chemical structure information and gene expression profiles of cell lines in a deep learning framework. For the first time, our model utilizes the largest known drug combination dataset to date, DrugComb. We compare the performance of MatchMaker with the state-of-the-art models and observe up to ~ 20% correlation and ~ 40% mean squared error (MSE) improvements over the next best method. We investigate the cell types and drug pairs that are relatively harder to predict and present novel candidate pairs. MatchMaker is built and available at https://github.com/tastanlab/matchmaker

scholarly journals Topology preserving stratification of tissue neoplasticity using Deep Neural Maps and microRNA signatures

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Emily Kaczmarek ◽  
Jina Nanayakkara ◽  
Alireza Sedghi ◽  
Mehran Pesteie ◽  
Thomas Tuschl ◽  
...  
Keyword(s):  
Deep Learning ◽  
Expression Profiles ◽  
Treatment Selection ◽  
Cancer Classification ◽  
Common Disease ◽  
Cancer Tissue ◽  
Topological Map ◽  
Tissue Samples ◽  
Learning Framework ◽  
Tissue Of Origin

Abstract Background Accurate cancer classification is essential for correct treatment selection and better prognostication. microRNAs (miRNAs) are small RNA molecules that negatively regulate gene expression, and their dyresgulation is a common disease mechanism in many cancers. Through a clearer understanding of miRNA dysregulation in cancer, improved mechanistic knowledge and better treatments can be sought. Results We present a topology-preserving deep learning framework to study miRNA dysregulation in cancer. Our study comprises miRNA expression profiles from 3685 cancer and non-cancer tissue samples and hierarchical annotations on organ and neoplasticity status. Using unsupervised learning, a two-dimensional topological map is trained to cluster similar tissue samples. Labelled samples are used after training to identify clustering accuracy in terms of tissue-of-origin and neoplasticity status. In addition, an approach using activation gradients is developed to determine the attention of the networks to miRNAs that drive the clustering. Using this deep learning framework, we classify the neoplasticity status of held-out test samples with an accuracy of 91.07%, the tissue-of-origin with 86.36%, and combined neoplasticity status and tissue-of-origin with an accuracy of 84.28%. The topological maps display the ability of miRNAs to recognize tissue types and neoplasticity status. Importantly, when our approach identifies samples that do not cluster well with their respective classes, activation gradients provide further insight in cancer subtypes or grades. Conclusions An unsupervised deep learning approach is developed for cancer classification and interpretation. This work provides an intuitive approach for understanding molecular properties of cancer and has significant potential for cancer classification and treatment selection.

scholarly journals Deep learning identifies synergistic drug combinations for treating COVID-19

2021 ◽  
Vol 118 (39) ◽  
pp. e2105070118
Author(s):  
Wengong Jin ◽  
Jonathan M. Stokes ◽  
Richard T. Eastman ◽  
Zina Itkin ◽  
Alexey V. Zakharov ◽  
...  
Keyword(s):  
Deep Learning ◽  
Drug Combination ◽  
Drug Target ◽  
Single Agent ◽  
Drug Combinations ◽  
Training Data ◽  
Biological Information ◽  
Target Interaction ◽  
Drug Synergy ◽  
Synergistic Drug Combinations

Effective treatments for COVID-19 are urgently needed. However, discovering single-agent therapies with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been challenging. Combination therapies play an important role in antiviral therapies, due to their improved efficacy and reduced toxicity. Recent approaches have applied deep learning to identify synergistic drug combinations for diseases with vast preexisting datasets, but these are not applicable to new diseases with limited combination data, such as COVID-19. Given that drug synergy often occurs through inhibition of discrete biological targets, here we propose a neural network architecture that jointly learns drug−target interaction and drug−drug synergy. The model consists of two parts: a drug−target interaction module and a target−disease association module. This design enables the model to utilize drug−target interaction data and single-agent antiviral activity data, in addition to available drug−drug combination datasets, which may be small in nature. By incorporating additional biological information, our model performs significantly better in synergy prediction accuracy than previous methods with limited drug combination training data. We empirically validated our model predictions and discovered two drug combinations, remdesivir and reserpine as well as remdesivir and IQ-1S, which display strong antiviral SARS-CoV-2 synergy in vitro. Our approach, which was applied here to address the urgent threat of COVID-19, can be readily extended to other diseases for which a dearth of chemical−chemical combination data exists.

scholarly journals Prediction of synergistic drug combinations using PCA-initialized deep learning

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jun Ma ◽  
Alison Motsinger-Reif
Keyword(s):  
Neural Network ◽  
Gene Expression ◽  
Machine Learning ◽  
Deep Learning ◽  
Drug Combination ◽  
Drug Combinations ◽  
Learning Approach ◽  
Drug Synergy ◽  
Machine Learning Methods ◽  
Synergistic Drug Combinations

Abstract Background Cancer is one of the main causes of death worldwide. Combination drug therapy has been a mainstay of cancer treatment for decades and has been shown to reduce host toxicity and prevent the development of acquired drug resistance. However, the immense number of possible drug combinations and large synergistic space makes it infeasible to screen all effective drug pairs experimentally. Therefore, it is crucial to develop computational approaches to predict drug synergy and guide experimental design for the discovery of rational combinations for therapy. Results We present a new deep learning approach to predict synergistic drug combinations by integrating gene expression profiles from cell lines and chemical structure data. Specifically, we use principal component analysis (PCA) to reduce the dimensionality of the chemical descriptor data and gene expression data. We then propagate the low-dimensional data through a neural network to predict drug synergy values. We apply our method to O’Neil’s high-throughput drug combination screening data as well as a dataset from the AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge. We compare the neural network approach with and without dimension reduction. Additionally, we demonstrate the effectiveness of our deep learning approach and compare its performance with three state-of-the-art machine learning methods: Random Forests, XGBoost, and elastic net, with and without PCA-based dimensionality reduction. Conclusions Our developed approach outperforms other machine learning methods, and the use of dimension reduction dramatically decreases the computation time without sacrificing accuracy.

scholarly journals Individual Tree Crown Segmentation Directly from UAV-Borne LiDAR Data Using the PointNet of Deep Learning

Forests ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 131
Author(s):  
Xinxin Chen ◽  
Kang Jiang ◽  
Yushi Zhu ◽  
Xiangjun Wang ◽  
Ting Yun
Keyword(s):  
Deep Learning ◽  
Mean Squared Error ◽  
Mixed Forest ◽  
Point Clouds ◽  
Forest Plot ◽  
Forest Types ◽  
Tree Crown ◽  
Individual Tree ◽  
Learning Framework ◽  
Crown Defoliation

Accurate individual tree crown (ITC) segmentation from scanned point clouds is a fundamental task in forest biomass monitoring and forest ecology management. Light detection and ranging (LiDAR) as a mainstream tool for forest survey is advancing the pattern of forest data acquisition. In this study, we performed a novel deep learning framework directly processing the forest point clouds belonging to the four forest types (i.e., the nursery base, the monastery garden, the mixed forest, and the defoliated forest) to realize the ITC segmentation. The specific steps of our approach were as follows: first, a voxelization strategy was conducted to subdivide the collected point clouds with various tree species from various forest types into many voxels. These voxels containing point clouds were taken as training samples for the PointNet deep learning framework to identify the tree crowns at the voxel scale. Second, based on the initial segmentation results, we used the height-related gradient information to accurately depict the boundaries of each tree crown. Meanwhile, the retrieved tree crown breadths of individual trees were compared with field measurements to verify the effectiveness of our approach. Among the four forest types, our results revealed the best performance for the nursery base (tree crown detection rate r = 0.90; crown breadth estimation R2 > 0.94 and root mean squared error (RMSE) < 0.2m). A sound performance was also achieved for the monastery garden and mixed forest, which had complex forest structures, complicated intersections of branches and different building types, with r = 0.85, R2 > 0.88 and RMSE < 0.6 m for the monastery garden and r = 0.80, R2 > 0.85 and RMSE < 0.8 m for the mixed forest. For the fourth forest plot type with the distribution of crown defoliation across the woodland, we achieved the performance with r = 0.82, R2 > 0.79 and RMSE < 0.7 m. Our method presents a robust framework inspired by the deep learning technology and computer graphics theory that solves the ITC segmentation problem and retrieves forest parameters under various forest conditions.

A Deep Learning Framework for Prediction of Retinal Disorders

2020 ◽  
Author(s):  
Raniyaharini R ◽  
Madhumitha K ◽  
Mishaa S ◽  
Virajaravi R
Keyword(s):  
Deep Learning ◽  
Learning Framework ◽  
Retinal Disorders

COVID-19 pneumonia diagnosis using a simple 2D deep learning framework with a single chest CT image (Preprint)

2020 ◽  
Author(s):  
Jinseok Lee
Keyword(s):  
Deep Learning ◽  
Diagnostic Performance ◽  
Ct Images ◽  
Chest Ct ◽  
University Hospital ◽  
Detection Accuracy ◽  
Ct Image ◽  
Test Dataset ◽  
Learning Framework ◽  
Testing Dataset

BACKGROUND The coronavirus disease (COVID-19) has explosively spread worldwide since the beginning of 2020. According to a multinational consensus statement from the Fleischner Society, computed tomography (CT) can be used as a relevant screening tool owing to its higher sensitivity for detecting early pneumonic changes. However, physicians are extremely busy fighting COVID-19 in this era of worldwide crisis. Thus, it is crucial to accelerate the development of an artificial intelligence (AI) diagnostic tool to support physicians. OBJECTIVE We aimed to quickly develop an AI technique to diagnose COVID-19 pneumonia and differentiate it from non-COVID pneumonia and non-pneumonia diseases on CT. METHODS A simple 2D deep learning framework, named fast-track COVID-19 classification network (FCONet), was developed to diagnose COVID-19 pneumonia based on a single chest CT image. FCONet was developed by transfer learning, using one of the four state-of-art pre-trained deep learning models (VGG16, ResNet50, InceptionV3, or Xception) as a backbone. For training and testing of FCONet, we collected 3,993 chest CT images of patients with COVID-19 pneumonia, other pneumonia, and non-pneumonia diseases from Wonkwang University Hospital, Chonnam National University Hospital, and the Italian Society of Medical and Interventional Radiology public database. These CT images were split into a training and a testing set at a ratio of 8:2. For the test dataset, the diagnostic performance to diagnose COVID-19 pneumonia was compared among the four pre-trained FCONet models. In addition, we tested the FCONet models on an additional external testing dataset extracted from the embedded low-quality chest CT images of COVID-19 pneumonia in recently published papers. RESULTS Of the four pre-trained models of FCONet, the ResNet50 showed excellent diagnostic performance (sensitivity 99.58%, specificity 100%, and accuracy 99.87%) and outperformed the other three pre-trained models in testing dataset. In additional external test dataset using low-quality CT images, the detection accuracy of the ResNet50 model was the highest (96.97%), followed by Xception, InceptionV3, and VGG16 (90.71%, 89.38%, and 87.12%, respectively). CONCLUSIONS The FCONet, a simple 2D deep learning framework based on a single chest CT image, provides excellent diagnostic performance in detecting COVID-19 pneumonia. Based on our testing dataset, the ResNet50-based FCONet might be the best model, as it outperformed other FCONet models based on VGG16, Xception, and InceptionV3.

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