Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, Le Quesne J, Moore DA, Veeriah S, Rosenthal R et al (2017) Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature 545:446–451

CAS  PubMed  PubMed Central  Google Scholar 

Baldi S, Korber P, Becker PB (2020) Beads on a string-nucleosome array arrangements and folding of the chromatin fiber. Nat Struct Mol Biol 27:109–118

CAS  PubMed  Google Scholar 

Baldi S, Krebs S, Blum H, Becker PB (2018) Genome-wide measurement of local nucleosome array regularity and spacing by nanopore sequencing. Nat Struct Mol Biol 25:894–901

CAS  PubMed  Google Scholar 

Bezdan D, Grigorev K, Meydan C, Pelissier Vatter FA, Cioffi M, Rao V, MacKay M, Nakahira K, Burnham P, Afshinnekoo E et al. 2020. Cell-free DNA (cfDNA) and exosome profiling from a year-long human spaceflight reveals circulating biomarkers. iScience 23: 101844.

Chandrananda D, Thorne NP, Bahlo M (2015) High-resolution characterization of sequence signatures due to non-random cleavage of cell-free DNA. BMC Med Genomics 8:29

PubMed  PubMed Central  Google Scholar 

Chereji RV, Kan TW, Grudniewska MK, Romashchenko AV, Berezikov E, Zhimulev IF, Guryev V, Morozov AV, Moshkin YM (2016) Genome-wide profiling of nucleosome sensitivity and chromatin accessibility in Drosophila melanogaster. Nucleic Acids Res 44:1036–1051

CAS  PubMed  Google Scholar 

Clarkson CT, Deeks EA, Samarista R, Mamayusupova H, Zhurkin VB, Teif VB (2019) CTCF-dependent chromatin boundaries formed by asymmetric nucleosome arrays with decreased linker length. Nucleic Acids Res 47:11181–11196

CAS  PubMed  PubMed Central  Google Scholar 

Cristiano S, Leal A, Phallen J, Fiksel J, Adleff V, Bruhm DC, Jensen SO, Medina JE, Hruban C, White JR et al (2019) Genome-wide cell-free DNA fragmentation in patients with cancer. Nature 570:385–389

CAS  PubMed  PubMed Central  Google Scholar 

Dawson MA, Kouzarides T (2012) Cancer epigenetics: from mechanism to therapy. Cell 150:12–27

CAS  PubMed  Google Scholar 

Diermeier S, Kolovos P, Heizinger L, Schwartz U, Georgomanolis T, Zirkel A, Wedemann G, Grosveld F, Knoch TA, Merkl R et al (2014) TNFalpha signalling primes chromatin for NF-kappaB binding and induces rapid and widespread nucleosome repositioning. Genome Biol 15:536

PubMed  PubMed Central  Google Scholar 

Dudley JC, Diehn M (2021) Detection and diagnostic utilization of cellular and cell-free tumor DNA. Annu Rev Pathol 16:199–222

Erger F, Norling D, Borchert D, Leenen E, Habbig S, Wiesener MS, Bartram MP, Wenzel A, Becker C, Toliat MR et al (2020) cfNOMe - a single assay for comprehensive epigenetic analyses of cell-free DNA. Genome Med 12:54

CAS  PubMed  PubMed Central  Google Scholar 

Frenel JS, Carreira S, Goodall J, Roda D, Perez-Lopez R, Tunariu N, Riisnaes R, Miranda S, Figueiredo I, Nava-Rodrigues D et al (2015) Serial next-generation sequencing of circulating cell-free DNA evaluating tumor clone response to molecularly targeted drug administration. Clin Cancer Res 21:4586–4596

CAS  PubMed  PubMed Central  Google Scholar 

Gaffney DJ, McVicker G, Pai AA, Fondufe-Mittendorf YN, Lewellen N, Michelini K, Widom J, Gilad Y, Pritchard JK (2012) Controls of nucleosome positioning in the human genome. PLoS Genet 8:e1003036

Guo J, Ma K, Bao H, Ma X, Xu Y, Wu X, Shao YW, Jiang M, Huang J (2020) Quantitative characterization of tumor cell-free DNA shortening. BMC Genomics 21:473

CAS  PubMed  PubMed Central  Google Scholar 

Han DSC, Ni M, Chan RWY, Chan VWH, Lui KO, Chiu RWK, Lo YMD (2020) The biology of cell-free DNA fragmentation and the roles of DNASE1, DNASE1L3, and DFFB. Am J Hum Genet 106:202–214

CAS  PubMed  PubMed Central  Google Scholar 

Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, Cheng JX, Murre C, Singh H, Glass CK (2010) Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell 38:576–589

CAS  PubMed  PubMed Central  Google Scholar 

Heitzer E, Auinger L, Speicher MR (2020) Cell-free DNA and apoptosis: how dead cells inform about the living. Trends Mol Med 26:519–528

CAS  Google Scholar 

Henikoff S, Church GM (2018) Simultaneous discovery of cell-free DNA and the nucleosome ladder. Genetics 209:27–29

CAS  PubMed  PubMed Central  Google Scholar 

Ho JW, Jung YL, Liu T, Alver BH, Lee S, Ikegami K, Sohn KA, Minoda A, Tolstorukov MY, Appert A et al (2014) Comparative analysis of metazoan chromatin organization. Nature 512:449–452

CAS  PubMed  PubMed Central  Google Scholar 

Hsieh TH, Weiner A, Lajoie B, Dekker J, Friedman N, Rando OJ (2015) Mapping nucleosome resolution chromosome folding in yeast by micro-C. Cell 162:108–119

CAS  PubMed  PubMed Central  Google Scholar 

Ignatiadis M, Sledge GW, Jeffrey SS (2021) Liquid biopsy enters the clinic - implementation issues and future challenges. Nat Rev Clin Oncol 18:297–312

Im YR, Tsui DWY, Diaz LA Jr, Wan JCM (2021) Next-generation liquid biopsies: embracing data science in oncology. Trends Cancer 7:283–292

Ioshikhes IP, Albert I, Zanton SJ, Pugh BF (2006) Nucleosome positions predicted through comparative genomics. Nat Genet 38:1210–1215

CAS  PubMed  Google Scholar 

Kananen L, Hurme M, Jylha M, Harkanen T, Koskinen S, Stenholm S, Kahonen M, Lehtimaki T, Ukkola O, Jylhava J (2020) Circulating cell-free DNA level predicts all-cause mortality independent of other predictors in the Health 2000 survey. Sci Rep 10:13809

CAS  PubMed  PubMed Central  Google Scholar 

Kitzman JO, Snyder MW, Ventura M, Lewis AP, Qiu R, Simmons LE, Gammill HS, Rubens CE, Santillan DA, Murray JC et al. 2012. Noninvasive whole-genome sequencing of a human fetus. Sci Transl Med 4: 137ra176.

Kundaje A, Kyriazopoulou-Panagiotopoulou S, Libbrecht M, Smith CL, Raha D, Winters EE, Johnson SM, Snyder M, Batzoglou S, Sidow A (2012) Ubiquitous heterogeneity and asymmetry of the chromatin environment at regulatory elements. Genome Res 22:1735–1747

CAS  PubMed  PubMed Central  Google Scholar 

Kustanovich A, Schwartz R, Peretz T, Grinshpun A (2019) Life and death of circulating cell-free DNA. Cancer Biol Ther 20:1057–1067

CAS  PubMed  PubMed Central  Google Scholar 

Langmead B, Trapnell C, Pop M, Salzberg SL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10:R25

PubMed  PubMed Central  Google Scholar 

Li C, Luscombe NM (2020) Nucleosome positioning stability is a modulator of germline mutation rate variation across the human genome. Nat Commun 11:1363

CAS  PubMed  PubMed Central  Google Scholar 

Liang J, Zhao W, Lu C, Liu D, Li P, Ye X, Zhao Y, Zhang J, Yang D. 2020. Next-generation sequencing analysis of ctDNA for the detection of glioma and metastatic brain tumors in adults. Front Neurol 11.

Liu MC, Oxnard GR, Klein EA, Swanton C, Seiden MV, Liu MC, Oxnard GR, Klein EA, Smith D, Richards D et al (2020) Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann Oncol 31:745–759

CAS  PubMed  Google Scholar 

Lo YMD, Han DSC, Jiang P, Chiu RWK. 2021. Epigenetics, fragmentomics, and topology of cell-free DNA in liquid biopsies. Science 372.

Ma X, Zhu L, Wu X, Bao H, Wang X, Chang Z, Shao YW, Wang Z. 2017. Cell-free DNA provides a good representation of the tumor genome despite its biased fragmentation patterns. PLoS One 12: e0169231.

Mallm JP, Iskar M, Ishaque N, Klett LC, Kugler SJ, Muino JM, Teif VB, Poos AM, Grossmann S, Erdel F et al. 2019. Linking aberrant chromatin features in chronic lymphocytic leukemia to transcription factor networks. Mol Syst Biol 15: e8339.

Mandel P, Metais P (1948) Les acides nucleiques du plasma sanguine chez l’homme. C R Seances Soc Biol Fil 142:241–243

CAS  PubMed  Google Scholar 

Markus H, Zhao J, Contente-Cuomo T, Stephens MD, Raupach E, Odenheimer-Bergman A, Connor S, McDonald BR, Moore B, Hutchins E et al (2021) Analysis of recurrently protected genomic regions in cell-free DNA found in urine. Sci Trans Med 13:eaaz3088

Mouliere F, Chandrananda D, Piskorz AM, Moore EK, Morris J, Ahlborn LB, Mair R, Goranova T, Marass F, Heider K et al. 2018a. Enhanced detection of circulating tumor DNA by fragment size analysis. Sci Transl Med 10.

Mouliere F, Mair R, Chandrananda D, Marass F, Smith CG, Su J, Morris J, Watts C, Brindle KM, Rosenfeld N. 2018b. Detection of cell-free DNA fragmentation and copy number alterations in cerebrospinal fluid from glioma patients. EMBO Mol Med 10.

Nassiri F, Chakravarthy A, Feng S, Shen SY, Nejad R, Zuccato JA, Voisin MR, Patil V, Horbinski C, Aldape K et al (2020) Detection and discrimination of intracranial tumors using plasma cell-free DNA methylomes. Nat Med 26:1044–1047

CAS  PubMed  PubMed Central  Google Scholar 

Ng H, Havervall S, Rosell A, Aguilera K, Parv K, von Meijenfeldt FA, Lisman T, Mackman N, Thålin C, Phillipson M (2021) Circulating markers of neutrophil extracellular traps are of prognostic value in patients with COVID-19. Arterioscler Thromb Vasc Biol 41:988–994

Palande V, Detroja R, Gorohovski A, Glass R, Flueh C, Kurtz M, Perez S, Shay DR, Siegal T, Frenkel-Morgenstern M (2020) A liquid biopsy platform for detecting gene-gene fusions as glioma diagnostic biomarkers and drug targets. bioRxiv 2020.02.25.963975

Parmar JJ, Padinhateeri R (2020) Nucleosome positioning and chromatin organization. Curr Opin Struct Biol 64:111–118

CAS  PubMed  Google Scholar 

Peng X, Li H-D, Wu F-X, Wang J (2021) Identifying the tissues-of-origin of circulating cell-free DNAs is a promising way in noninvasive diagnostics. Brief Bioinform 22:bbaa060

Phallen J, Sausen M, Adleff V, Leal A, Hruban C, White J, Anagnostou V, Fiksel J, Cristiano S, Papp E et al. 2017. Direct detection of early-stage cancers using circulating tumor DNA. Sci Transl Med 9.

Pich O, Muinos F, Sabarinathan R, Reyes-Salazar I, Gonzalez-Perez A, Lopez-Bigas N. 2018. Somatic and germline mutation periodicity follow the orientation of the DNA minor groove around nucleosomes. Cell 175: 1074–1087 e1018.

Ramachandran S, Ahmad K, Henikoff S. 2017. Transcription and remodeling produce asymmetrically unwrapped nucleosomal intermediates. Mol Cell 68: 1038–1053 e1034.

Ramesh N, Sei E, Tsai PC, Bai S, Zhao Y, Troncoso P, Corn PG, Logothetis C, Zurita AJ, Navin NE (2020) Decoding the evolutionary response to prostate cancer therapy by plasma genome sequencing. Genome Biol 21:162

CAS  PubMed  PubMed Central  Google Scholar 

Rostami A, Lambie M, Yu CW, Stambolic V, Waldron JN, Bratman SV. 2020. Senescence, necrosis, and apoptosis govern circulating cell-free DNA release kinetics. Cell Rep 31: 107830.

Schones DE, Cui K, Cuddapah S, Roh TY, Barski A, Wang Z, Wei G, Zhao K (2008) Dynamic regulation of nucleosome positioning in the human genome. Cell 132:887–898

CAS  Google Scholar 

Segal E, Fondufe-Mittendorf Y, Chen L, Thastrom A, Field Y, Moore IK, Wang JP, Widom J (2006) A genomic code for nucleosome positioning. Nature 442:772–778

CAS  PubMed  PubMed Central  Google Scholar 

Serpas L, Chan RWY, Jiang P, Ni M, Sun K, Rashidfarrokhi A, Soni C, Sisirak V, Lee WS, Cheng SH et al (2019) Dnase1l3 deletion causes aberrations in length and end-motif frequencies in plasma DNA. Proc Natl Acad Sci U S A 116:641–649

CAS  PubMed  Google Scholar 

Shen SY, Singhania R, Fehringer G, Chakravarthy A, Roehrl MHA, Chadwick D, Zuzarte PC, Borgida A, Wang TT, Li T et al (2018) Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Nature 563:579–583

CAS  PubMed  Google Scholar 

Snyder MW, Kircher M, Hill AJ, Daza RM, Shendure J (2016) Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin. Cell 164:57–68

CAS  PubMed  PubMed Central  Google Scholar 

Song C-X, Yin S, Ma L, Wheeler A, Chen Y, Zhang Y, Liu B, Xiong J, Zhang W, Hu J et al (2017) 5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages. Cell Res 27:1231–1242

CAS  PubMed  PubMed Central  Google Scholar 

Stergachis AB, Debo BM, Haugen E, Churchman LS, Stamatoyannopoulos JA (2020) Single-molecule regulatory architectures captured by chromatin fiber sequencing. Science 368:1449–1454

CAS  PubMed  Google Scholar 

Sun K, Jiang P, Wong AIC, Cheng YKY, Cheng SH, Zhang H, Chan KCA, Leung TY, Chiu RWK, Lo YMD (2018) Size-tagged preferred ends in maternal plasma DNA shed light on the production mechanism and show utility in noninvasive prenatal testing. Proc Natl Acad Sci U S A 115:E5106-e5114

CAS  PubMed