DRUG-NEM: Optimizing drug combinations using single-cell perturbation response to account for intratumoral heterogeneity
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作者:
Anchang, Benedict
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Stanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USAStanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USA
Anchang, Benedict
[1
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Davis, Kara L.
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Stanford Univ, Dept Pediat, Div Hematol & Oncol, Stanford, CA 94305 USAStanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USA
Davis, Kara L.
[2
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Fienberg, Harris G.
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Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USAStanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USA
Fienberg, Harris G.
[3
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Williamson, Brian D.
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Stanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USAStanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USA
Williamson, Brian D.
[1
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Bendall, Sean C.
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Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USAStanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USA
Bendall, Sean C.
[4
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Karacosta, Loukia G.
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Stanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USAStanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USA
Karacosta, Loukia G.
[1
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Tibshirani, Robert
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Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA
Stanford Univ, Dept Stat, Stanford, CA 94305 USAStanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USA
Tibshirani, Robert
[5
,6
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Nolan, Garry P.
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Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USAStanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USA
Nolan, Garry P.
[3
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Plevritis, Sylvia K.
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Stanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USA
Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USAStanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USA
Plevritis, Sylvia K.
[1
,5
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机构:
[1] Stanford Univ, Dept Radiol, Ctr Canc Syst Biol, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Pediat, Div Hematol & Oncol, Stanford, CA 94305 USA
[3] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA
[4] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA
[5] Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA
[6] Stanford Univ, Dept Stat, Stanford, CA 94305 USA
An individual malignant tumor is composed of a heterogeneous collection of single cells with distinct molecular and phenotypic features, a phenomenon termed intratumoral heterogeneity. Intratumoral heterogeneity poses challenges for cancer treatment, motivating the need for combination therapies. Single-cell technologies are now available to guide effective drug combinations by accounting for intratumoral heterogeneity through the analysis of the signaling perturbations of an individual tumor sample screened by a drug panel. In particular, Mass Cytometry Time-of-Flight (CyTOF) is a high-throughput single-cell technology that enables the simultaneous measurements of multiple (>40) intracellular and surface markers at the level of single cells for hundreds of thousands of cells in a sample. We developed a computational framework, entitled Drug Nested Effects Models (DRUG-NEM), to analyze CyTOF single-drug perturbation data for the purpose of individualizing drug combinations. DRUG-NEM optimizes drug combinations by choosing the minimum number of drugs that produce the maximal desired intracellular effects based on nested effects modeling. We demonstrate the performance of DRUG-NEM using single-cell drug perturbation data from tumor cell lines and primary leukemia samples.
机构:
Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Ferdowsi Univ Mashhad, Dept Anim Sci, Mashhad, IranKarolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Mohammadi, Elyas
Dashti, Samira
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Mashhad Univ Med Sci, Dept Internal Med, Mashhad, IranKarolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Dashti, Samira
Shafizade, Neda
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Mashhad Univ Med Sci, Dept Internal Med, Mashhad, IranKarolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Shafizade, Neda
Jin, Han
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机构:
KTH Royal Inst Technol, Sci Life Lab, Stockholm, SwedenKarolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Jin, Han
Zhang, Cheng
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KTH Royal Inst Technol, Sci Life Lab, Stockholm, SwedenKarolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Zhang, Cheng
Lam, Simon
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Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, EnglandKarolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Lam, Simon
Tahmoorespur, Mojtaba
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机构:
Ferdowsi Univ Mashhad, Dept Anim Sci, Mashhad, IranKarolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Tahmoorespur, Mojtaba
Mardinoglu, Adil
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机构:
KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden
Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London, EnglandKarolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Mardinoglu, Adil
Sekhavati, Mohammad Hadi
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Ferdowsi Univ Mashhad, Dept Anim Sci, Mashhad, IranKarolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
机构:
Univ Southern Calif, Thomas Lord Dept Comp Sci, 941 Bloom Walk, Los Angeles, CA 90089 USAUniv Southern Calif, Thomas Lord Dept Comp Sci, 941 Bloom Walk, Los Angeles, CA 90089 USA
Liu, Sizhe
Chen, Liang
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Univ Southern Calif, Dept Quantitat & Computat Biol, 1050 Childs Way, Los Angeles, CA 90089 USAUniv Southern Calif, Thomas Lord Dept Comp Sci, 941 Bloom Walk, Los Angeles, CA 90089 USA
机构:
City Univ Hong Kong, Dept Comp Sci, Kowloon, Hong Kong, Peoples R ChinaCity Univ Hong Kong, Dept Comp Sci, Kowloon, Hong Kong, Peoples R China
Zheng, Zetian
Chen, Junyi
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Lab Data Discovery Hlth D4H, Hong Kong Sci Pk, Hong Kong, Peoples R ChinaCity Univ Hong Kong, Dept Comp Sci, Kowloon, Hong Kong, Peoples R China
Chen, Junyi
Chen, Xingjian
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City Univ Hong Kong, Dept Comp Sci, Kowloon, Hong Kong, Peoples R ChinaCity Univ Hong Kong, Dept Comp Sci, Kowloon, Hong Kong, Peoples R China
Chen, Xingjian
Huang, Lei
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City Univ Hong Kong, Dept Comp Sci, Kowloon, Hong Kong, Peoples R ChinaCity Univ Hong Kong, Dept Comp Sci, Kowloon, Hong Kong, Peoples R China
Huang, Lei
Xie, Weidun
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City Univ Hong Kong, Dept Comp Sci, Kowloon, Hong Kong, Peoples R ChinaCity Univ Hong Kong, Dept Comp Sci, Kowloon, Hong Kong, Peoples R China
Xie, Weidun
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机构:
Lin, Qiuzhen
Li, Xiangtao
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Jilin Univ, Sch Artificial Intelligence, Jilin, Peoples R ChinaCity Univ Hong Kong, Dept Comp Sci, Kowloon, Hong Kong, Peoples R China
Li, Xiangtao
Wong, Ka-Chun
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机构:
City Univ Hong Kong, Dept Comp Sci, Kowloon, Hong Kong, Peoples R China
City Univ Hong Kong, Shenzhen Res Inst, Shenzhen, Peoples R China
City Univ Hong Kong, Hong Kong Inst Data Sci, Hong Kong, Peoples R ChinaCity Univ Hong Kong, Dept Comp Sci, Kowloon, Hong Kong, Peoples R China