Inference of transcription factor binding from cell-free DNA enables tumor subtype prediction and early detection.

Abstract:

:Deregulation of transcription factors (TFs) is an important driver of tumorigenesis, but non-invasive assays for assessing transcription factor activity are lacking. Here we develop and validate a minimally invasive method for assessing TF activity based on cell-free DNA sequencing and nucleosome footprint analysis. We analyze whole genome sequencing data for >1,000 cell-free DNA samples from cancer patients and healthy controls using a bioinformatics pipeline developed by us that infers accessibility of TF binding sites from cell-free DNA fragmentation patterns. We observe patient-specific as well as tumor-specific patterns, including accurate prediction of tumor subtypes in prostate cancer, with important clinical implications for the management of patients. Furthermore, we show that cell-free DNA TF profiling is capable of detection of early-stage colorectal carcinomas. Our approach for mapping tumor-specific transcription factor binding in vivo based on blood samples makes a key part of the noncoding genome amenable to clinical analysis.

journal_name

Nat Commun

journal_title

Nature communications

authors

Ulz P,Perakis S,Zhou Q,Moser T,Belic J,Lazzeri I,Wölfler A,Zebisch A,Gerger A,Pristauz G,Petru E,White B,Roberts CES,John JS,Schimek MG,Geigl JB,Bauernhofer T,Sill H,Bock C,Heitzer E,Speicher MR

doi

10.1038/s41467-019-12714-4

subject

Has Abstract

pub_date

2019-10-11 00:00:00

pages

4666

issue

1

issn

2041-1723

pii

10.1038/s41467-019-12714-4

journal_volume

10

pub_type

杂志文章
  • Reciprocal regulation of the Il9 locus by counteracting activities of transcription factors IRF1 and IRF4.

    abstract::The T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of signals induced by cytokines and antigen presentation. Here we show that, within this network, two interferon regulatory factors (IRF), IRF1 and IRF4, display opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, wherea...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms15366

    authors: Campos Carrascosa L,Klein M,Kitagawa Y,Lückel C,Marini F,König A,Guralnik A,Raifer H,Hagner-Benes S,Rädler D,Böck A,Kang C,Lohoff M,Garn H,Schaub B,Berberich-Siebelt F,Sakaguchi S,Bopp T,Huber M

    更新日期:2017-05-12 00:00:00

  • Epigenetic dysregulation of enhancers in neurons is associated with Alzheimer's disease pathology and cognitive symptoms.

    abstract::Epigenetic control of enhancers alters neuronal functions and may be involved in Alzheimer's disease (AD). Here, we identify enhancers in neurons contributing to AD by comprehensive fine-mapping of DNA methylation at enhancers, genome-wide. We examine 1.2 million CpG and CpH sites in enhancers in prefrontal cortex neu...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-10101-7

    authors: Li P,Marshall L,Oh G,Jakubowski JL,Groot D,He Y,Wang T,Petronis A,Labrie V

    更新日期:2019-05-21 00:00:00

  • Task complexity interacts with state-space uncertainty in the arbitration between model-based and model-free learning.

    abstract::It has previously been shown that the relative reliability of model-based and model-free reinforcement-learning (RL) systems plays a role in the allocation of behavioral control between them. However, the role of task complexity in the arbitration between these two strategies remains largely unknown. Here, using a com...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-13632-1

    authors: Kim D,Park GY,O Doherty JP,Lee SW

    更新日期:2019-12-16 00:00:00

  • The formation and evolution of Titan's winter polar vortex.

    abstract::Saturn's largest moon Titan has a substantial nitrogen-methane atmosphere, with strong seasonal effects, including formation of winter polar vortices. Following Titan's 2009 northern spring equinox, peak solar heating moved to the northern hemisphere, initiating south-polar subsidence and winter polar vortex formation...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01839-z

    authors: Teanby NA,Bézard B,Vinatier S,Sylvestre M,Nixon CA,Irwin PGJ,de Kok RJ,Calcutt SB,Flasar FM

    更新日期:2017-11-21 00:00:00

  • A Pseudomonas T6SS effector recruits PQS-containing outer membrane vesicles for iron acquisition.

    abstract::Iron sequestration by host proteins contributes to the defence against bacterial pathogens, which need iron for their metabolism and virulence. A Pseudomonas aeruginosa mutant lacking all three known iron acquisition systems retains the ability to grow in media containing iron chelators, suggesting the presence of add...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms14888

    authors: Lin J,Zhang W,Cheng J,Yang X,Zhu K,Wang Y,Wei G,Qian PY,Luo ZQ,Shen X

    更新日期:2017-03-28 00:00:00

  • Confidence controls perceptual evidence accumulation.

    abstract::Perceptual decisions are accompanied by feelings of confidence that reflect the likelihood that the decision was correct. Here we aim to clarify the relationship between perception and confidence by studying the same perceptual task across three different confidence contexts. Human observers were asked to categorize t...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15561-w

    authors: Balsdon T,Wyart V,Mamassian P

    更新日期:2020-04-09 00:00:00

  • Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression.

    abstract::Metabolic reprogramming greatly contributes to the regulation of macrophage activation. However, the mechanism of lipid accumulation and the corresponding function in tumor-associated macrophages (TAMs) remain unclear. With primary investigation in colon cancer and confirmation in other cancer models, here we determin...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-04999-8

    authors: Xiang W,Shi R,Kang X,Zhang X,Chen P,Zhang L,Hou A,Wang R,Zhao Y,Zhao K,Liu Y,Ma Y,Luo H,Shang S,Zhang J,He F,Yu S,Gan L,Shi C,Li Y,Yang W,Liang H,Miao H

    更新日期:2018-07-03 00:00:00

  • Metal-free dehydropolymerisation of phosphine-boranes using cyclic (alkyl)(amino)carbenes as hydrogen acceptors.

    abstract::The divalent carbene carbon centre in cyclic (alkyl)(amino)carbenes (CAACs) is known to exhibit transition-metal-like insertion into E-H σ-bonds (E = H, N, Si, B, P, C, O) with formation of new, strong C-E and C-H bonds. Although subsequent transformations of the products represent an attractive strategy for metal-fre...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-08967-8

    authors: Oldroyd NL,Chitnis SS,Annibale VT,Arz MI,Sparkes HA,Manners I

    更新日期:2019-03-26 00:00:00

  • Photoswitchable semiconductor nanocrystals with self-regulating photochromic Förster resonance energy transfer acceptors.

    abstract::Photoswitchable molecules and nanoparticles constitute superior biosensors for a wide range of industrial, research and biomedical applications. Rendered reversible by spontaneous or deterministic means, such probes facilitate many of the techniques in fluorescence microscopy that surpass the optical resolution dictat...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7036

    authors: Díaz SA,Gillanders F,Jares-Erijman EA,Jovin TM

    更新日期:2015-01-16 00:00:00

  • Tailoring nanoscopic confines to maximize catalytic activity of hydronium ions.

    abstract::Acid catalysis by hydronium ions is ubiquitous in aqueous-phase organic reactions. Here we show that hydronium ion catalysis, exemplified by intramolecular dehydration of cyclohexanol, is markedly influenced by steric constraints, yielding turnover rates that increase by up to two orders of magnitude in tight confines...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms15442

    authors: Shi H,Eckstein S,Vjunov A,Camaioni DM,Lercher JA

    更新日期:2017-05-25 00:00:00

  • Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation.

    abstract::Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms10872

    authors: Li D,Liu J,Guo B,Liang C,Dang L,Lu C,He X,Cheung HY,Xu L,Lu C,He B,Liu B,Shaikh AB,Li F,Wang L,Yang Z,Au DW,Peng S,Zhang Z,Zhang BT,Pan X,Qian A,Shang P,Xiao L,Jiang B,Wong CK,Xu J,Bian Z,Liang Z,

    更新日期:2016-03-07 00:00:00

  • The Par3 polarity protein is an exocyst receptor essential for mammary cell survival.

    abstract::The exocyst is an essential component of the secretory pathway required for delivery of basolateral proteins to the plasma membranes of epithelial cells. Delivery occurs adjacent to tight junctions (TJ), suggesting that it recognizes a receptor at this location. However, no such receptor has been identified. The Par3 ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms14867

    authors: Ahmed SM,Macara IG

    更新日期:2017-03-30 00:00:00

  • Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia.

    abstract::The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells th...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7200

    authors: Liou GY,Döppler H,Braun UB,Panayiotou R,Scotti Buzhardt M,Radisky DC,Crawford HC,Fields AP,Murray NR,Wang QJ,Leitges M,Storz P

    更新日期:2015-02-20 00:00:00

  • Theory of Floquet band formation and local pseudospin textures in pump-probe photoemission of graphene.

    abstract::Ultrafast materials science promises optical control of physical properties of solids. Continuous-wave circularly polarized laser driving was predicted to induce a light-matter coupled state with an energy gap and a quantum Hall effect, coined Floquet topological insulator. Whereas the envisioned Floquet topological i...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms8047

    authors: Sentef MA,Claassen M,Kemper AF,Moritz B,Oka T,Freericks JK,Devereaux TP

    更新日期:2015-05-11 00:00:00

  • Drug and disease signature integration identifies synergistic combinations in glioblastoma.

    abstract::Glioblastoma (GBM) is the most common primary adult brain tumor. Despite extensive efforts, the median survival for GBM patients is approximately 14 months. GBM therapy could benefit greatly from patient-specific targeted therapies that maximize treatment efficacy. Here we report a platform termed SynergySeq to identi...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07659-z

    authors: Stathias V,Jermakowicz AM,Maloof ME,Forlin M,Walters W,Suter RK,Durante MA,Williams SL,Harbour JW,Volmar CH,Lyons NJ,Wahlestedt C,Graham RM,Ivan ME,Komotar RJ,Sarkaria JN,Subramanian A,Golub TR,Schürer SC,Ayad NG

    更新日期:2018-12-14 00:00:00

  • Low-grade chromosomal mosaicism in human somatic and embryonic stem cell populations.

    abstract::Current knowledge on chromosomal mosaicism in human cell cultures is mostly based on cytogenetic banding methods. The recent development of high-resolution full-genome analysis methods applicable to single cells is providing new insights into genetic and cellular diversity. Here we study the genetic content of 92 indi...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5227

    authors: Jacobs K,Mertzanidou A,Geens M,Nguyen HT,Staessen C,Spits C

    更新日期:2014-06-27 00:00:00

  • DNA replication timing and higher-order nuclear organization determine single-nucleotide substitution patterns in cancer genomes.

    abstract::Single-nucleotide substitutions are a defining characteristic of cancer genomes. Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified. Here we propose that DNA replication patterns help shape the mutational landscapes of normal and can...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms2502

    authors: Liu L,De S,Michor F

    更新日期:2013-01-01 00:00:00

  • The cascading origin of the 2018 Kīlauea eruption and implications for future forecasting.

    abstract::The 2018 summit and flank eruption of Kīlauea Volcano was one of the largest volcanic events in Hawai'i in 200 years. Data suggest that a backup in the magma plumbing system at the long-lived Pu'u 'Ō'ō eruption site caused widespread pressurization in the volcano, driving magma into the lower flank. The eruption evolv...

    journal_title:Nature communications

    pub_type: 杂志文章,评审

    doi:10.1038/s41467-020-19190-1

    authors: Patrick MR,Houghton BF,Anderson KR,Poland MP,Montgomery-Brown E,Johanson I,Thelen W,Elias T

    更新日期:2020-11-06 00:00:00

  • Coherence and modality of driven interlayer-coupled magnetic vortices.

    abstract::The high-frequency dynamics of mode-coupled magnetic vortices have generated great interest for spintronic technologies, such as spin-torque nano-oscillators. While the spectroscopic characteristics of vortex oscillators have been reported, direct imaging of driven coupled magnetic quasi-particles is essential to the ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4760

    authors: Pulecio JF,Warnicke P,Pollard SD,Arena DA,Zhu Y

    更新日期:2014-04-30 00:00:00

  • Direct observation of dynamic charge stripes in La2-xSrxNiO4.

    abstract::The insulator-to-metal transition continues to be a challenging subject, especially when electronic correlations are strong. In layered compounds, such as La2-xSrxNiO4 and La2-xBaxCuO4, the doped charge carriers can segregate into periodically spaced charge stripes separating narrow domains of antiferromagnetic order....

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4467

    authors: Anissimova S,Parshall D,Gu GD,Marty K,Lumsden MD,Chi S,Fernandez-Baca JA,Abernathy DL,Lamago D,Tranquada JM,Reznik D

    更新日期:2014-03-17 00:00:00

  • ROW1 maintains quiescent centre identity by confining WOX5 expression to specific cells.

    abstract::The quiescent centre (QC) in the Arabidopsis root apical meristem is essential for stem cell organization. Here we show that the loss of REPRESSOR OF WUSCHEL1 (ROW1), a PHD domain-containing protein, leads to QC failure, defects in cell differentiation and ectopic expression of WUSCHEL-RELATED HOMEOBOX 5 (WOX5) in cel...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7003

    authors: Zhang Y,Jiao Y,Liu Z,Zhu YX

    更新日期:2015-01-29 00:00:00

  • Self-assembled nanoscale coordination polymers with trigger release properties for effective anticancer therapy.

    abstract::Nanoscale coordination polymers (NCPs) are self-assembled from metal ions and organic bridging ligands, and can overcome many drawbacks of existing drug delivery systems by virtue of tunable compositions, sizes and shapes, high drug loadings, ease of surface modification and intrinsic biodegradability. Here we report ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5182

    authors: Liu D,Poon C,Lu K,He C,Lin W

    更新日期:2014-06-25 00:00:00

  • STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters.

    abstract::Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-19684-y

    authors: Boudewijns R,Thibaut HJ,Kaptein SJF,Li R,Vergote V,Seldeslachts L,Van Weyenbergh J,De Keyzer C,Bervoets L,Sharma S,Liesenborghs L,Ma J,Jansen S,Van Looveren D,Vercruysse T,Wang X,Jochmans D,Martens E,Roose K,De Vlie

    更新日期:2020-11-17 00:00:00

  • A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals.

    abstract::Metabolism is coordinated among tissues and organs via neuronal signals. Levels of circulating amino acids (AAs), which are elevated in obesity, activate the intracellular target of rapamycin complex-1 (mTORC1)/S6kinase (S6K) pathway in the liver. Here we demonstrate that hepatic AA/mTORC1/S6K signalling modulates sys...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms8940

    authors: Uno K,Yamada T,Ishigaki Y,Imai J,Hasegawa Y,Sawada S,Kaneko K,Ono H,Asano T,Oka Y,Katagiri H

    更新日期:2015-08-13 00:00:00

  • Mapping ecologically relevant social behaviours by gene knockout in wild mice.

    abstract::The laboratory mouse serves as an important model system for studying gene, brain and behavioural interactions. Powerful methods of gene targeting have helped to decipher gene-function associations in human diseases. Yet, the laboratory mouse, obtained after decades of human-driven artificial selection, inbreeding, an...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5569

    authors: Chalfin L,Dayan M,Levy DR,Austad SN,Miller RA,Iraqi FA,Dulac C,Kimchi T

    更新日期:2014-08-05 00:00:00

  • Structure of a microtubule-bound axonemal dynein.

    abstract::Axonemal dyneins are tethered to doublet microtubules inside cilia to drive ciliary beating, a process critical for cellular motility and extracellular fluid flow. Axonemal dyneins are evolutionarily and biochemically distinct from cytoplasmic dyneins that transport cargo, and the mechanisms regulating their localizat...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-20735-7

    authors: Walton T,Wu H,Brown A

    更新日期:2021-01-20 00:00:00

  • Three-dimensional protonic conductivity in porous organic cage solids.

    abstract::Proton conduction is a fundamental process in biology and in devices such as proton exchange membrane fuel cells. To maximize proton conduction, three-dimensional conduction pathways are preferred over one-dimensional pathways, which prevent conduction in two dimensions. Many crystalline porous solids to date show one...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms12750

    authors: Liu M,Chen L,Lewis S,Chong SY,Little MA,Hasell T,Aldous IM,Brown CM,Smith MW,Morrison CA,Hardwick LJ,Cooper AI

    更新日期:2016-09-13 00:00:00

  • Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction.

    abstract::Members of the interleukin-1 (IL-1) family are important mediators of obesity and metabolic disease and have been described to often play opposing roles. Here we report that the interleukin-36 (IL-36) subfamily can play a protective role against the development of disease. Elevated IL-36 cytokine expression is found i...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-11944-w

    authors: Giannoudaki E,Hernandez-Santana YE,Mulfaul K,Doyle SL,Hams E,Fallon PG,Mat A,O'Shea D,Kopf M,Hogan AE,Walsh PT

    更新日期:2019-09-05 00:00:00

  • Human immunoglobulin G hinge regulates agonistic anti-CD40 immunostimulatory and antitumour activities through biophysical flexibility.

    abstract::Human immunoglobulin G (IgG) agonistic antibodies targeting costimulatory immunoreceptors represent promising cancer immunotherapies yet to be developed. Whether, and how, human IgG hinge and Fc impact on their agonistic functions have been disputed. Here, we show that different natural human IgGs confer divergent ago...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-12097-6

    authors: Liu X,Zhao Y,Shi H,Zhang Y,Yin X,Liu M,Zhang H,He Y,Lu B,Jin T,Li F

    更新日期:2019-09-27 00:00:00

  • Acquisition, transmission and strain diversity of human gut-colonizing crAss-like phages.

    abstract::CrAss-like phages are double-stranded DNA viruses that are prevalent in human gut microbiomes. Here, we analyze gut metagenomic data from mother-infant pairs and patients undergoing fecal microbiota transplantation to evaluate the patterns of acquisition, transmission and strain diversity of crAss-like phages. We find...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-14103-3

    authors: Siranosian BA,Tamburini FB,Sherlock G,Bhatt AS

    更新日期:2020-01-15 00:00:00