scholarly journals Personalized single-cell networks: a framework to predict the response of any gene to any drug for any patient

2020 ◽  
Author(s):  
HARIPRIYA HARIKUMAR ◽  
Thomas P Quinn ◽  
Santu Rana ◽  
Sunil Gupta ◽  
Svetha Venkatesh
Keyword(s):  
Single Cell ◽  
Drug Response ◽  
Single Cells ◽  
Biological Data ◽  
Patient Specific ◽  
Expression Data ◽  
Drug Responses ◽  
Dual Channel ◽  
Cell Gene ◽  
Cell Networks

Abstract Background: The last decade has seen a major increase in the availability of genomic data. This includes expert-curated databases that describe the biological activity of genes, as well as high-throughput assays that measure gene expression in bulk tissue and single cells. Integrating these heterogeneous data sources can generate new hypotheses about biological systems. Our primary objective is to combine population-level drug-response data with patient-level single-cell expression data to predict how any gene will respond to any drug for any patient.Methods: We take 2 approaches to benchmarking a “dual-channel” random walk with restart (RWR) for data integration. First, we evaluate how well RWR can predict known gene functions from single-cell gene co-expression networks. Second, we evaluate how well RWR can predict known drug responses from individual cell networks. We then present two exploratory applications. In the first application, we combine the Gene Ontology database with glioblastoma single cells from 5 individual patients to identify genes whose functions differ between cancers. In the second application, we combine the LINCS drug-response database with the same glioblastoma data to identify genes that may exhibit patient-specific drug responses.Conclusions: Our manuscript introduces two innovations to the integration of heterogeneous biological data. First, we use a “dual-channel” method to predict up-regulation and down-regulation separately. Second, we use individualized single-cell gene co-expression networks to make personalized predictions. These innovations let us predict gene function and drug response for individual patients. Taken together, our work shows promise that single-cell co-expression data could be combined in heterogeneous information networks to facilitate precision medicine.

scholarly journals Personalized single-cell networks: a framework to predict the response of any gene to any drug for any patient

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Haripriya Harikumar ◽  
Thomas P. Quinn ◽  
Santu Rana ◽  
Sunil Gupta ◽  
Svetha Venkatesh
Keyword(s):  
Single Cell ◽  
Drug Response ◽  
Single Cells ◽  
Biological Data ◽  
Patient Specific ◽  
Expression Data ◽  
Drug Responses ◽  
Dual Channel ◽  
Cell Gene ◽  
Cell Networks

Abstract Background The last decade has seen a major increase in the availability of genomic data. This includes expert-curated databases that describe the biological activity of genes, as well as high-throughput assays that measure gene expression in bulk tissue and single cells. Integrating these heterogeneous data sources can generate new hypotheses about biological systems. Our primary objective is to combine population-level drug-response data with patient-level single-cell expression data to predict how any gene will respond to any drug for any patient. Methods We take 2 approaches to benchmarking a “dual-channel” random walk with restart (RWR) for data integration. First, we evaluate how well RWR can predict known gene functions from single-cell gene co-expression networks. Second, we evaluate how well RWR can predict known drug responses from individual cell networks. We then present two exploratory applications. In the first application, we combine the Gene Ontology database with glioblastoma single cells from 5 individual patients to identify genes whose functions differ between cancers. In the second application, we combine the LINCS drug-response database with the same glioblastoma data to identify genes that may exhibit patient-specific drug responses. Conclusions Our manuscript introduces two innovations to the integration of heterogeneous biological data. First, we use a “dual-channel” method to predict up-regulation and down-regulation separately. Second, we use individualized single-cell gene co-expression networks to make personalized predictions. These innovations let us predict gene function and drug response for individual patients. Taken together, our work shows promise that single-cell co-expression data could be combined in heterogeneous information networks to facilitate precision medicine.

scholarly journals Personalized Single-Cell Networks: A Framework to Predict The Response of Any Gene To Any Drug For Any Patient

2020 ◽  
Author(s):  
Haripriya Harikumar ◽  
Thomas P Quinn ◽  
Santu Rana ◽  
Sunil Gupta ◽  
Svetha Venkatesh
Keyword(s):  
Single Cell ◽  
Drug Response ◽  
Single Cells ◽  
Heterogeneous Data ◽  
Primary Objective ◽  
Biological Data ◽  
Patient Specific ◽  
Specific Drug ◽  
Integrated Network ◽  
Dual Channel

Abstract Background: The last decade has seen a major increase in the availability of genomic data. This includes expert-curated databases that describe the biological activity of genes, as well as high-throughput assays that measure the gene expression of bulk tissue and single cells. Integrating these heterogeneous data sources can generate new hypotheses about biological systems. Our primary objective is to combine population-level drug-response data with patient-level single-cell expression data to predict how any gene will respond to any drug for any patient. Methods: We use a “dual-channel” random walk with restart algorithm to perform 3 analyses. First, we use glioblastoma single cells from 5 individual patients to discover genes whose functions differ between cancers. Second, we use drug screening data from the Library of Integrated Network-Based Cellular Signatures (LINCS) to show how a cell-specific drug-response signature can be accurately predicted from a baseline (drug-free) gene co-expression network. Finally, we combine both data streams to show how we can predict how any gene will respond to any drug for each of the 5 glioblastoma patients. Conclusions: Our manuscript introduces two innovations to the integration of heterogeneous biological data. First, we use a “dual-channel” method to predict up-regulation and down-regulation separately. Second, we use individualized single-cell gene co-expression networks to make personalized predictions. These innovations let us predict gene function and drug response for individual patients. When applied to real data, we identify a number of genes that exhibit a patient-specific drug response, including the pan-cancer oncogene EGFR.

scholarly journals A random walk down personalized single-cell networks: predicting the response of any gene to any drug for any patient

2019 ◽  
Author(s):  
Haripriya Harikumar ◽  
Thomas P. Quinn ◽  
Santu Rana ◽  
Sunil Gupta ◽  
Svetha Venkatesh
Keyword(s):  
Random Walk ◽  
Single Cell ◽  
Drug Response ◽  
Single Cells ◽  
Heterogeneous Data ◽  
Primary Objective ◽  
Biological Data ◽  
Patient Specific ◽  
Specific Drug ◽  
Dual Channel

AbstractBackgroundThe last decade has seen a major increase in the availability of genomic data. This includes expert-curated databases that describe the biological activity of genes, as well as high-throughput assays that measure the gene expression of bulk tissue and single cells. Integrating these heterogeneous data sources can generate new hypotheses about biological systems. Our primary objective is to combine population-level drug-response data with patient-level single-cell expression data to predict how any gene will respond to any drug for any patient.MethodsWe use a “dual-channel” random walk with restart (RWR) algorithm to perform 3 analyses. First, we use glioblastoma single cells from 5 individual patients to discover genes whose functions differ between cancers. Second, we use drug screening data from the Library of Integrated Network-Based Cellular Signatures (LINCS) to show how a cell-specific drug-response signature can be accurately predicted from a baseline (drug-free) gene co-expression network. Finally, we combine both data streams to show how the RWR algorithm can predict how any gene will respond to any drug for each of the 5 glioblastoma patients.ConclusionsOur manuscript introduces two innovations to the integration of heterogeneous biological data. First, we use a “dual-channel” RWR method to predict up-regulation and down-regulation separately. Second, we use individualized single-cell gene co-expression networks to make personalized predictions. These innovations let us predict gene function and drug response for individual patients. When applied to real data, we identify a number of genes that exhibit a patient-specific drug response, including the pan-cancer oncogene EGFR.

scholarly journals Deep Transfer Learning of Drug Sensitivity by Integrating Bulk and Single-cell RNA-seq data

2021 ◽  
Author(s):  
Junyi Chen ◽  
Ren Qi ◽  
Zhenyu Wu ◽  
Anjun Ma ◽  
Lang Li ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Transfer Learning ◽  
Large Scale ◽  
Drug Response ◽  
Single Cells ◽  
Cancer Drug ◽  
Sequencing Data ◽  
Drug Responses ◽  
Single Cell Rna Sequencing

Massively bulk RNA sequencing databases incorporating drug screening have opened up an avenue to inform the optimal clinical application of cancer drugs. Meanwhile, the growing single-cell RNA sequencing data contributes to improving therapeutic effectiveness by studying the heterogeneity of drug responses for cancer cell subpopulations. Yet, the drug response information for single-cell data is scarcely obtained. Thus, there is an urgent need to develop computational pipelines to infer and interpret cancer drug responses in single cells. Here, we developed scDEAL, a deep transfer learning framework integrating large-scale bulk and single-cell RNA sequencing drug response datasets. We benchmarked scDEAL on six single-cell RNA sequencing datasets and indicate its model interpretability by several case studies. scDEAL not only achieves accurate and robust performance in single-cell drug response predictions, but also can infer signature genes to reveal potential drug resistance mechanisms based on integrated gradient feature interpretation. This work may help study cell reprogramming, drug selection, and repurposing for improving therapeutic efficacy.

scholarly journals Microfluidics 3D gel-island chip for single cell isolation and lineage-dependent drug responses study

Lab on a Chip ◽  
2016 ◽  
Vol 16 (13) ◽  
pp. 2504-2512 ◽  
Author(s):  
Zhixiong Zhang ◽  
Yu-Chih Chen ◽  
Yu-Heng Cheng ◽  
Yi Luan ◽  
Euisik Yoon
Keyword(s):  
Single Cell ◽  
Drug Response ◽  
Cell Tracking ◽  
Single Cells ◽  
Cell Isolation ◽  
Microfluidic Platform ◽  
Drug Responses ◽  
3D Microenvironment ◽  
Single Cell Isolation

This paper reports a novel gel-island microfluidic platform enabling single-cell tracking in biomimetic 3D microenvironment for investigating heterogeneous drug response of single cells.

scholarly journals SOMSC: Self-Organization-Map for High-Dimensional Single-Cell Data of Cellular States and Their Transitions

2017 ◽  
Author(s):  
Tao Peng ◽  
Qing Nie
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Gene Expression Data ◽  
Single Cells ◽  
High Dimensional ◽  
Expression Data ◽  
Rna Seq ◽  
Cell Gene Expression ◽  
Cell Data ◽  
Cell Gene

AbstractMeasurement of gene expression levels for multiple genes in single cells provides a powerful approach to study heterogeneity of cell populations and cellular plasticity. While the expression levels of multiple genes in each cell are available in such data, the potential connections among the cells (e.g. the cellular state transition relationship) are not directly evident from the measurement. Classifying the cellular states, identifying their transitions among those states, and extracting the pseudotime ordering of cells are challenging due to the noise in the data and the high-dimensionality in the number of genes in the data. In this paper we adapt the classical self-organizing-map (SOM) approach for single-cell gene expression data (SOMSC), such as those based on single cell qPCR and single cell RNA-seq. In SOMSC, a cellular state map (CSM) is derived and employed to identify cellular states inherited in the population of the measured single cells. Cells located in the same basin of the CSM are considered as in one cellular state while barriers among the basins in CSM provide information on transitions among the cellular states. A cellular state transitions path (e.g. differentiation) and a temporal ordering of the measured single cells are consequently obtained. In addition, SOMSC could estimate the cellular state replication probability and transition probabilities. Applied to a set of synthetic data, one single-cell qPCR data set on mouse early embryonic development and two single-cell RNA-seq data sets, SOMSC shows effectiveness in capturing cellular states and their transitions presented in the high-dimensional single-cell data. This approach will have broader applications to analyzing cellular fate specification and cell lineages using single cell gene expression data

scholarly journals Graph Convolutional Network for Drug Response Prediction Using Gene Expression Data

Mathematics ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 772
Author(s):  
Seonghun Kim ◽  
Seockhun Bae ◽  
Yinhua Piao ◽  
Kyuri Jo
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Large Scale ◽  
Drug Response ◽  
Response Prediction ◽  
Biological Data ◽  
Expression Data ◽  
Convolutional Network ◽  
Essential Information ◽  
Protein Protein Interaction

Genomic profiles of cancer patients such as gene expression have become a major source to predict responses to drugs in the era of personalized medicine. As large-scale drug screening data with cancer cell lines are available, a number of computational methods have been developed for drug response prediction. However, few methods incorporate both gene expression data and the biological network, which can harbor essential information about the underlying process of the drug response. We proposed an analysis framework called DrugGCN for prediction of Drug response using a Graph Convolutional Network (GCN). DrugGCN first generates a gene graph by combining a Protein-Protein Interaction (PPI) network and gene expression data with feature selection of drug-related genes, and the GCN model detects the local features such as subnetworks of genes that contribute to the drug response by localized filtering. We demonstrated the effectiveness of DrugGCN using biological data showing its high prediction accuracy among the competing methods.

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