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公开(公告)号：US20230014674A1
公开(公告)日：2023-01-19
申请号：US17290924
申请日：2019-11-07
Applicant: Cancer Research Technology Limited
Inventor： Florent Mouliere , Dineika Chandrananda , Anna Piskorz , James Brenton , Nitzan Rosenfeld
Abstract: The present invention provides a computer-implemented method for detecting variant nucleic acid from a cell-free nucleic acid-containing sample. The method comprises (a) providing data representing fragment sizes of nucleic acid fragments obtained from said sample and/or representing a measure of deviation from copy number neutrality of the nucleic acid fragments obtained from said sample; b) processing the data from step a) according to a classification algorithm, wherein said classification algorithm operates to classify sample data into one of at least a first class containing the variant nucleic acid and a second class not containing the variant nucleic acid, based on a plurality of cell-free nucleic acid fragment size features and/or a deviation from copy number neutrality feature; and c) outputting the classification of the sample from step b, thereby determining whether the sample contains the variant nucleic acid or not, or a probability that the sample contains the variant nucleic acid. Related methods are also provided.
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公开(公告)号：US20220017891A1
公开(公告)日：2022-01-20
申请号：US17295338
申请日：2019-11-22
Applicant: Cancer Research Technology Limited
Inventor： Katrin Heider , Jonathan Wan , Nitzan Rosenfeld
IPC: C12N15/10 , C12Q1/6806
Abstract: The present invention provides a method for detecting variant cell-free DNA (cfDNA) in a sample obtained from a subject, where analysis of the sample includes a size-selection step which separates out different fragment sizes of DNA. The sample may be a limited volume sample such as a blood, serum or plasma sample of less than 500 μl (e.g. a blood or plasma sample of about 50 μl), or other sample that has a low content of cfDNA. The sample may have been stored and/or dried and not have been processed to remove cells or cellular material prior to storage. The size-selection step may comprise filtering-out, depleting or removing genomic DNA (gDNA) fragments of >200 bp, >300 bp, >500 bp, >700 bp, >1000 bp, >1200 bp, >1500 bp, or >2000 bp prior to analysis, e.g. prior to DNA sequencing. The method may further comprise performing an analysis that summarises or combines data across multiple loci.
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公开(公告)号：US20170204455A1
公开(公告)日：2017-07-20
申请号：US15325046
申请日：2015-07-17
Applicant: Cancer Research Technology Limited
Inventor： Nitzan Rosenfeld , Tim Forshew , Francesco Marass , Muhammed Murtaza
CPC classification number: C12Q1/6858 , C12Q1/6827 , C12Q1/6883 , C12Q1/6886 , C12Q2527/146 , C12Q2537/165 , C12Q2600/106 , C12Q2600/118 , C12Q2600/156 , G16B20/00 , C12Q2535/122 , C12Q2545/114 , C12Q2563/159
Abstract: The present invention provides a method for detecting a genetic variant in a region of interest in a DNA sample comprising (i) determining, for a given sequencing platform, sequencing process and sequencing depth, the distribution of the number of reads supporting a genetic variant or plurality of genetic variants expected to be observed in the sequencing results of amplification reactions due to amplification and sequencing error (read count distribution); (ii) based on the read count distribution determined in step (i), establishing a threshold frequency at or above which the genetic variant must be observed in sequencing results of amplification reactions to assign a positive determination for the presence of the genetic variant in a given amplification reaction; (iii) partitioning the DNA sample into a plurality of replicate amplification reactions, so that the mean number of amplifiable template molecules of the region of interest in a replicate amplification reaction is fewer than the reciprocal of the threshold frequency determined in step (ii); (iv) performing the amplification reactions of step (iii) and sequencing the products of amplification reactions, (v) based on step (ii) and the results of step (iv), determining the presence/absence of the genetic variant in each replicate amplification reaction; and (vi) integrating the results of (v) to determine the presence/absence of the genetic variant in the region of interest in the DNA sample.
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4.发明申请公开(公告)号：US20200232021A1
公开(公告)日：2020-07-23
申请号：US16749923
申请日：2020-01-22
Applicant: Cancer Research Technology Limited
Inventor： Nitzan Rosenfeld , Tim Forshew , Francesco Marass , Muhammed Murtaza
IPC: C12Q1/6858 , C12Q1/6827 , C12Q1/6886 , C12Q1/6883 , G16B20/00
Abstract: The present invention provides a method for detecting a genetic variant in a region of interest in a DNA sample comprising (i) determining, for a given sequencing platform, sequencing process and sequencing depth, the distribution of the number of reads supporting a genetic variant or plurality of genetic variants expected to be observed in the sequencing results of amplification reactions due to amplification and sequencing error (read count distribution); (ii) based on the read count distribution determined in step (i), establishing a threshold frequency at or above which the genetic variant must be observed in sequencing results of amplification reactions to assign a positive determination for the presence of the genetic variant in a given amplification reaction; (iii) partitioning the DNA sample into a plurality of replicate amplification reactions, so that the mean number of amplifiable template molecules of the region of interest in a replicate amplification reaction is fewer than the reciprocal of the threshold frequency determined in step (ii); (iv) performing the amplification reactions of step (iii) and sequencing the products of amplification reactions, (v) based on step (ii) and the results of step (iv), determining the presence/absence of the genetic variant in each replicate amplification reaction; and (vi) integrating the results of (v) to determine the presence/absence of the genetic variant in the region of interest in the DNA sample.
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