87:, among other features. While the CLiP method is unique in relying exclusively on mutations and copy number alterations, it is related to a variety of other liquid biopsy methods being commercially developed for early cancer detection using ctDNA and proteins (e.g., CancerSEEK / DETECT-A ), cfDNA fragmentation patterns (e.g., DELFI), and DNA methylation (e.g., cfMeDIP-Seq, Grail).
54:(ctDNA). The CLiP technique integrates multiple distinctive genomic features of a cancer of interest findings within a machine-learning framework for cancer detection. For example, studies have shown that the majority of somatic mutations found in cell-free DNA (cfDNA) are not tumor derived, but instead reflect
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While the CLiP method has not yet been broadly applied for population-based cancer screening, it has been shown to distinguish discriminate early-stage lung cancers from risk-matched controls across multiple cohorts of patients enrolled across the US.
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can be distinguished from CHIP-derived mutations. This is because unlike tumor-derived mutations, CHIP-derived mutations that are shed from leukocytes into plasma tend to occur on longer cfDNA fragments, and to lack specific
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Chabon, Jacob J.; Hamilton, Emily G.; Kurtz, David M.; Esfahani, Mohammad S.; Moding, Everett J.; Stehr, Henning; Schroers-Martin, Joseph; Nabet, Barzin Y.; Chen, Binbin; Chaudhuri, Aadel A.; Liu, Chih Long (April 2020).
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Newman, Aaron M.; Bratman, Scott V.; To, Jacqueline; Wynne, Jacob F.; Eclov, Neville C. W.; Modlin, Leslie A.; Liu, Chih Long; Neal, Joel W.; Wakelee, Heather A.; Merritt, Robert E.; Shrager, Joseph B. (May 2014).
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Razavi, Pedram; Li, Bob T.; Brown, David N.; Jung, Byoungsok; Hubbell, Earl; Shen, Ronglai; Abida, Wassim; Juluru, Krishna; De Bruijn, Ino; Hou, Chenlu; Venn, Oliver (December 2019).
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such as those associated with tobacco smoking in lung cancer that are also found in tumor derived ctDNA molecules. CLiP integrates these features within hierarchical ensemble
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and detected in cfDNA, regardless of whether profiling patients with cancer and healthy adults. However, genuine tumor derived
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methods for integrating various genomic features useful for the noninvasive detection of early cancers from blood
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tends to target specific genes, it also involves many generally non-recurrent mutations that can be shed from
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This method relies on several improvements to cancer personalized profiling by deep sequencing (
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Shen, Shu Yi; Burgener, Justin M.; Bratman, Scott V.; De
Carvalho, Daniel D. (October 2019).
404:"DNA blood test spots cancers in seemingly cancer-free women, but also produces false alarms"
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27:. An application of this technique for early detection of
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31:(Lung-CLiP) was originally described by
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555:Sample, Ian (2020-03-25).
19:(CLiP) refers to a set of
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191:10.1038/s41586-020-2140-0
135:10.4249/scholarpedia.2776
85:copy number alternations
79:models that consider
73:mutational signatures
52:circulating tumor DNA
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183:2020Natur.580..245C
126:2009SchpJ...4.2776P
110:"Ensemble learning"
531:"Pathfinder Study"
50:) for analysis of
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64:leukocytes
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