Disease-specific motifs can be identified in circulating nucleic acids from live elk and cattle infected with transmissible spongiform encephalopathies

Gordon, Paul M.; Schütz, Ekkehard; Beck, Julia; Urnovitz, Howard B.; Graham, Catherine; Clark, Renee; Dudas, Sandor; Czub, Stefanie; Sensen, Maria; Brenig, Bertram; Groschup, Martin H.; Church, Robert B.; Sensen, Christoph Wilhelm

doi:10.1093/nar/gkn963

Cited by 19 publications

(23 citation statements)

References 40 publications

(38 reference statements)

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“…7 In our analysis Hs17 is significantly overrepresented as a source of DNA motifs in relapsing MS patients versus control subjects with three distinct chromosomal hot spots. These results confirm the value of MSA technologies to detect informative serum DNA biomarkers that we have reported recently in experimental neurodegenerative diseases of cattle 8,9 and elk. 9 …”

Section: All Ms Parn(ϩ) Commd10(ϩ) Tmem117(ϩ) Spag17(ϫ) Neb(ϫ) Psupporting

confidence: 90%

“…These results confirm the value of MSA technologies to detect informative serum DNA biomarkers that we have reported recently in experimental neurodegenerative diseases of cattle 8,9 and elk. 9 …”

Section: All Ms Parn(ϩ) Commd10(ϩ) Tmem117(ϩ) Spag17(ϫ) Neb(ϫ) Psupporting

confidence: 90%

“…The ecotropic viral integration site, EVI1, is predictive of the progressive spongiform encephalopathy observed in chronic wasting disease of elk. 9 Other endogenous retroviral elements have been similarly observed in bovine spongiform encephalopathy. 8,9 EVI1 is recognized also as the CCR7 chemokine receptor gene.…”

Section: Discussionmentioning

confidence: 98%

“…9 Other endogenous retroviral elements have been similarly observed in bovine spongiform encephalopathy. 8,9 EVI1 is recognized also as the CCR7 chemokine receptor gene. The EVI1/CCR7 gene is important in that human endogenous retrovirus (HERV) peptides in the expression of type 1 cytokine profiles in vitro of peripheral blood mononuclear cells from patients in relapsing phases of MS but not from stable MS patients have been reported.…”

Section: Discussionmentioning

confidence: 98%

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Serum DNA Motifs Predict Disease and Clinical Status in Multiple Sclerosis

Beck¹,

Urnovitz²,

Saresella³

et al. 2010

The Journal of Molecular Diagnostics

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Using recently available mass sequencing and assembly technologies , we have been able to identify and quantify unique cell-free DNA motifs in the blood of patients with multiple sclerosis (MS). The most common MS clinical syndrome , relapsing-remitting MS (RRMS) , is accompanied by a unique fingerprint of both inter-and intragenic cell-free circulating nucleic acids as specific DNA sequences that provide significant clinical sensitivity and specificity. Coding genes that are differentially represented in MS serum encode cytoskeletal proteins, brain-expressed regulators of growth, and receptors involved in nervous system signal transduction. Although coding genes distinguish RRMS and its clinical activity, several repeat sequences, such as the L1M family of LINE elements, are consistently different in all MS patients and clinical status versus the normal database. These data demonstrate that DNA motifs observed in serum are characteristic of RRMS and disease activity and are promising as a clinical tool in monitoring patient responses to treatment modalities.

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Section: All Ms Parn(ϩ) Commd10(ϩ) Tmem117(ϩ) Spag17(ϫ) Neb(ϫ) Psupporting

confidence: 90%

Section: All Ms Parn(ϩ) Commd10(ϩ) Tmem117(ϩ) Spag17(ϫ) Neb(ϫ) Psupporting

confidence: 90%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

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Serum DNA Motifs Predict Disease and Clinical Status in Multiple Sclerosis

Beck¹,

Urnovitz²,

Saresella³

et al. 2010

The Journal of Molecular Diagnostics

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“…The method has been validated for trisomies 13,18, and 21 as a clinical laboratory procedure with a remarkable diagnostic accuracy Ͼ99% (32 ). The statistical power provided by NGS platforms through massive parallel sequencing coupled with mass assembly [mass sequence and assembly (MSA)] allowed us to report algorithms predictive of variant Creutzfeldt-Jakob in ruminantia (33,34 ) and multiple sclerosis (35 ) and breast cancer (14,36 ) in humans with- Boxes (interquartile ranges) and whiskers (5th and 95th percentiles) are shown together with the median (black horizontal line) of the investigated groups.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal Instability in Cell-Free DNA Is a Serum Biomarker for Prostate Cancer

Schütz¹,

Akbari

Beck³

et al. 2015

Clinical Chemistry

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BACKGROUND Genomic instability resulting in copy number variation is a hallmark of malignant transformation and may be identified through massive parallel sequencing. Tumor-specific cell free DNA (cfDNA) present in serum and plasma provides a real-time, easily accessible surrogate. METHODS DNA was extracted from serum of 204 patients with prostate cancer (Gleason score 2–10), 207 male controls, and patients with benign hyperplasia (n = 10) and prostatitis (n = 10). DNA was amplified by use of random primers, tagged with molecular identifiers, sequenced on a SOLID system, and aligned to the human genome. We evaluated the number of sequence reads of cfDNA in sliding 100-kbp intervals for variation from controls. We used chromosomal regions with significant variations in alignment hits for their ability to segregate patients and matched controls. RESULTS Using ROC curves to assess diagnostic performance, we evaluated the number of regions in a first subset (n = 177), with variations in alignment hits alone, provided an area under the curve (AUC) of 0.81 (95% CI 0.7–0.9, P < 0.001). Using 5 rounds of 10-fold cross-validation with the full data set, we established a final model that discriminated prostate cancer from controls with an AUC of 0.92 (0.87–0.95), reaching a diagnostic accuracy of 83%. Both benign prostatic hypertrophy and prostatitis could be distinguished from prostate cancer by use of cfDNA, with an accuracy of 90%. CONCLUSIONS Assessment of a limited number of chromosomal structural instabilities by use of massive parallel sequencing of cfDNA was sufficient to distinguish between prostate cancer and controls. This large cohort demonstrates the utility of cfDNA in prostate cancer recently established in other malignant neoplasms.

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Plasma nucleic acid analysis by massively parallel sequencing: pathological insights and diagnostic implications

Chiu

2011

The Journal of Pathology

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Over the past 15 years there has been increasing interest in the biology and diagnostic applications of circulating DNA in the plasma of human subjects. In particular, DNA from a fetus, a tumour, a transplanted organ and injured tissues has been found in the plasma of pregnant women, cancer patients, transplant recipients and patients suffering from multiple pathologies, respectively. The advent of massively parallel sequencing has given us a quantitative and powerful tool for studying circulating DNA on a genome-wide level. Using this approach, fetal chromosomal aneuploidies can be robustly detected using maternal plasma. Furthermore, a genome-wide genetic map of a fetus can also be constructed using this approach. This method has also allowed one to identify tumour-associated chromosomal translocations, which can then be detected in plasma. The direct application of massively parallel sequencing to the serum of cancer patients has also allowed quantitative aberrations that are associated with malignancy to be detected in serum. The use of massively parallel sequencing on the plasma of transplantation recipients has opened up an approach for detecting rejection. The application of circulating DNA sequencing has also opened up a new method for elucidating the quantitative aberration of circulating DNA in many pathological conditions. Such developments would provide new modalities for molecular diagnostics and would improve our understanding of the biology of circulating nucleic acids.

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Disease-specific motifs can be identified in circulating nucleic acids from live elk and cattle infected with transmissible spongiform encephalopathies

Cited by 19 publications

References 40 publications

Serum DNA Motifs Predict Disease and Clinical Status in Multiple Sclerosis

Serum DNA Motifs Predict Disease and Clinical Status in Multiple Sclerosis

Chromosomal Instability in Cell-Free DNA Is a Serum Biomarker for Prostate Cancer

Plasma nucleic acid analysis by massively parallel sequencing: pathological insights and diagnostic implications

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