Inferring gene expression from cell-free DNA fragmentation profiles

被引：121

作者：

Esfahani, Mohammad Shahrokh ^{[1
,2
,3
,4
]}

Hamilton, Emily G. ^{[5
]}

Mehrmohamadi, Mahya ^{[1
,2
,3
]}

Nabet, Barzin Y. ^{[3
,4
]}

Alig, Stefan K. ^{[1
,2
]}

King, Daniel A. ^{[1
,2
]}

Steen, Chloe B. ^{[1
,2
,6
,7
]}

Macaulay, Charles W. ^{[1
,2
]}

Schultz, Andre ^{[4
]}

Nesselbush, Monica C. ^{[5
]}

Soo, Joanne ^{[1
,2
]}

Schroers-Martin, Joseph G. ^{[1
,2
,4
]}

Chen, Binbin ^{[1
,2
]}

Binkley, Michael S. ^{[3
]}

Stehr, Henning ^{[4
]}

Chabon, Jacob J. ^{[3
]}

Sworder, Brian J. ^{[1
,2
]}

Hui, Angela B-Y ^{[3
]}

Frank, Matthew J. ^{[8
]}

Moding, Everett J. ^{[3
]}

Liu, Chih Long ^{[1
,2
]}

Newman, Aaron M. ^{[6
,7
]}

Isbell, James M. ^{[9
,10
]}

Rudin, Charles M. ^{[11
]}

Li, Bob T. ^{[11
]}

Kurtz, David M. ^{[1
,2
,4
]}

Diehn, Maximilian ^{[3
,4
,6
]}

Alizadeh, Ash A. ^{[1
,2
,4
,6
]}

机构：

[1] Stanford Sch Med, Dept Med, Div Oncol, Stanford, CA 94305 USA

[2] Stanford Sch Med, Dept Med, Div Hematol, Stanford, CA 94305 USA

[3] Stanford Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA

[4] Stanford Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA

[5] Stanford Sch Med, Program Canc Biol, Stanford, CA 94305 USA

[6] Stanford Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[7] Stanford Sch Med, Dept Biomed Informat, Stanford, CA 94305 USA

[8] Stanford Sch Med, Dept Med, Div Blood & Marrow Transplantat & Cellular Therap, Stanford, CA 94305 USA

[9] Mem Sloan Kettering Canc Ctr, Thorac Surg Serv, 1275 York Ave, New York, NY 10021 USA

[10] Weill Cornell Med, New York, NY USA

[11] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA

来源：

NATURE BIOTECHNOLOGY | 2022年 / 40卷 / 04期

基金：

美国国家卫生研究院;

关键词：

LUNG-CANCER; PLASMA DNA; NONINVASIVE DETECTION; PROGNOSTIC IMPACT; LYMPHOMA; TUMOR; CLASSIFICATION; CHEMOTHERAPY; METHYLATION; PREDICTION;

D O I：

10.1038/s41587-022-01222-4

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

EPIC-seq predicts expression of individual genes from cell-free DNA. Profiling of circulating tumor DNA (ctDNA) in the bloodstream shows promise for noninvasive cancer detection. Chromatin fragmentation features have previously been explored to infer gene expression profiles from cell-free DNA (cfDNA), but current fragmentomic methods require high concentrations of tumor-derived DNA and provide limited resolution. Here we describe promoter fragmentation entropy as an epigenomic cfDNA feature that predicts RNA expression levels at individual genes. We developed 'epigenetic expression inference from cell-free DNA-sequencing' (EPIC-seq), a method that uses targeted sequencing of promoters of genes of interest. Profiling 329 blood samples from 201 patients with cancer and 87 healthy adults, we demonstrate classification of subtypes of lung carcinoma and diffuse large B cell lymphoma. Applying EPIC-seq to serial blood samples from patients treated with PD-(L)1 immune-checkpoint inhibitors, we show that gene expression profiles inferred by EPIC-seq are correlated with clinical response. Our results indicate that EPIC-seq could enable noninvasive, high-throughput tissue-of-origin characterization with diagnostic, prognostic and therapeutic potential.

引用

页码：585 / +

页数：27

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