Search

Your search keyword '"Simpson, J.T."' showing total 21 results
Start Over Author "Simpson, J.T."
21 results on '"Simpson, J.T."'

3. A community effort to create standards for evaluating tumor subclonal reconstruction

Author

Salcedo, A., Tarabichi, M., Espiritu, S.M.G., Deshwar, A.G., David, M., Wilson, N.M., Dentro, S., Wintersinger, J.A., Liu, L.Y., Ko, M., Sivanandan, S., Zhang, H., Zhu, K., Ou Yang, T.-H., Chilton, J.M., Buchanan, A., Lalansingh, C.M., P’ng, C., Anghel, C.V., Umar, I., Lo, B., Zou, W., Jha, A., Huang, T., Yang, T.-P., Peifer, M., Sahinalp, C., Malikic, S., Vázquez-García, I., Mustonen, V., Yang, H.-T., Lee, K.-R., Ji, Y., Sengupta, Subhajit, Rudewicz, J., Nikolski, M., Schaeverbeke, Q., Yuan, K., Markowetz, F., Macintyre, G., Cmero, M., Chaudhary, B., Leshchiner, I., Livitz, D., Getz, G., Loher, P., Yu, K., Wang, W., Zhu, H., Simpson, J.T., Stuart, J.M., Anastassiou, D., Guan, Y., Ewing, A.D., Ellrott, K., Wedge, D.C., Morris, Q., Van Loo, P., Boutros, P.C., Department of Ecology and Evolutionary Biology [University of Toronto] (EEB), University of Toronto, Pennsylvania State University (Penn State), Penn State System, The Wellcome Trust Sanger Institute [Cambridge], Capital Normal University [Beijing], University of Queensland [Brisbane], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford [Oxford], Department of Computer Science, Helsinki Institute for Information Technology, Bioinformatics, Institute of Biotechnology, and Organismal and Evolutionary Biology Research Programme

Subjects
DNA Copy Number Variations, Tumour heterogeneity, Computer science, 3122 Cancers, Gene Dosage, Biomedical Engineering, Inference, Bioengineering, Computational biology, Polymorphism, Single Nucleotide, Applied Microbiology and Biotechnology, Genome, Tumor heterogeneity, Article, DNA sequencing, 03 medical and health sciences, 0302 clinical medicine, GENOME SIMULATION, Neoplasms, Humans, HETEROGENEITY, Computer Simulation, SOMATIC POINT MUTATIONS, Evolutionary dynamics, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, 318 Medical biotechnology, IDENTIFICATION, Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc, Reference Standards, CANCER, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], EVOLUTION, Clone Cells, 3. Good health, Cancer evolution, Mutation, Mutation (genetic algorithm), Molecular Medicine, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Algorithms, 030217 neurology & neurosurgery, Biotechnology
Abstract

Tumor DNA sequencing data can be interpreted by computational methods that analyse genomic heterogeneity to infer evolutionary dynamics. A growing number of studies have used these approaches to link cancer evolution with clinical progression and response to therapy. Although the inference of tumor phylogenies is rapidly becoming standard practice in cancer genome analyses, standards for evaluating tumor phylogenies are lacking. To address this need, we systematically assess methods for reconstructing tumor sub-clonality. First, we elucidate the main algorithmic problems in subclonal reconstruction and develop quantitative metrics for evaluating them. Then we simulate realistic tumor genomes that harbor all known clonal and subclonal mutation types and processes. We benchmark 580 tumor reconstructions, varying tumor read-depth, tumour type, and somatic variant detection. Our analysis provides a baseline for the establishment of gold-standard methods to analyze tumor heterogeneity., Editors summary Methods for reconstructing tumor evolution are benchmarked in the DREAM Somatic Mutation Calling Tumour Heterogeneity Challenge using novel tools.

Published
2020
Full Text
View/download PDF

4. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Author

Bailey, M.H., Meyerson, W.U., Dursi, L.J., Wang, L.B., Dong, G., Liang, W.W., Weerasinghe, A., Li, S., Li, Y., Kelso, S., Saksena, G., Ellrott, K., Wendl, M.C., Wheeler, D.A., Getz, G., Simpson, J.T., Gerstein, M.B., and Ding, Li

Subjects
Cancer Research
Abstract

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF

Published
2020

8. Deep short-read sequencing of chromosome 17 from the mouse strains A/J and CAST/Ei identifies significant germline variation and candidate genes that regulate liver triglyceride levels

Author

Sudbery, I., Stalker, J., Simpson, J.T., Keane, T., Rust, A.G., Hurles, M.E., Walter, K., Lynch, D., Teboul, L., Brown, S.D., Li, H., Ning, Z., Nadeau, J.H., Croniger, C.M., Durbin, R., and Adams, D.J.

Subjects
animal diseases, food and beverages
Abstract

Genome sequences are essential tools for comparative and mutational analyses. Here we present the short read sequence of mouse chromosome 17 from the Mus musculus domesticus derived strain A/J, and the Mus musculus castaneus derived strain CAST/Ei. We describe approaches for the accurate identification of nucleotide and structural variation in the genomes of vertebrate experimental organisms, and show how these techniques can be applied to help prioritize candidate genes within quantitative trait loci.

Published
2009

13. Pentafluorobenzyl chloroformate derivatization for enhancement of detection of amino acids or alcohols by electron capture negative ion chemical ionization mass spectrometry

Author

Simpson, J.T., Torok, D.S., and Markey, S.P.

Abstract

Pentafluorobenzyl chloroformate (PFB-chloroformate) has been utilized as a derivatization reagent to impart electron affinity and provide structurally relevant fragmentation in electron capture negative ion chemical ionization mass spectrometry (ECNICI-MS). Phenylalanine (Phe) and decanol were used as model analytes. The conditions used for their derivatization and the chromatographic and mass spectrometric properties of the derivatives are reported. Phenylalanine in aqueous solution was derivatized in one step by using PFB-chloroformate and a mixture of water, ethanol, and pyridine. The phenylalanine N-pentafluorobenzyl-oxycarbonyl ethyl ester (N-PFBC-Phe-OEt) exhibited good gas chromatographic properties and in ECNICI-MS, a dominant [M — 181]−fragment carries most of the ion current. Selected ion monitoring experiments on N-PFBC-Phe-OEt resulted in the facile detection of 400 fmol of material. Decanol was derivatized by using anhydrous conditions, and the resultant pentafluorobenzyl carbonate also exhibited a predominant [M — 181]−ion in ECNICI-MS. Initial results indicate that the ECNICI-MS molar response of the decyl pentafluorobenzyl carbonate derivative is six-fold that of the decyl pentafluorobenzoate.

Published
1995
Full Text
View/download PDF

14. Characterization of anthraquinone-2-carbonyl chloride as an alcohol derivatization reagent for negative ion chemical ionization mass spectrometry

Author

Simpson, J.T., Torok, D.S., Worman, R., Quearry, B.J., Markey, S.P., and Ziffer, H.

Abstract

Anthraquinone-2-carbonyl chloride has been utilized as a derivatization reagent for alcohols to impart electron affinity and aid in transport via a particle beam liquid chromatography—mass spectrometry (LC/MS) interface. In addition, the gas chromatographic—mass spectrometry, UV, fluorescence, and electrochemical characteristics of the derivatives were determined. A series of model compounds, 2-phenylethanol (phenethyl alcohol), 1-phenyl-2-propanol, 2-methyl-1-phenyl-2-propanol, hexanol, and methyl 2-methylglycerate, were used as analytes.

Published
1995
Full Text
View/download PDF

15. Nanopore sequencing and assembly of a human genome with ultra-long reads

Author

Jain, M., Koren, S., Miga, K.H., Quick, J., Rand, A.C., Sasani, T.A., Tyson, J.R., Beggs, A.D., Dilthey, A.T., Fiddes, I.T., Malla, S., Marriott, H., Nieto, T., O'Grady, J., Olsen, H.E., Pedersen, B.S., Rhie, A., Richardson, H., Quinlan, A.R., Snutch, T.P., Tee, L., Paten, B., Phillippy, A.M., Simpson, J.T., Loman, N.J., Loose, M., Jain, M., Koren, S., Miga, K.H., Quick, J., Rand, A.C., Sasani, T.A., Tyson, J.R., Beggs, A.D., Dilthey, A.T., Fiddes, I.T., Malla, S., Marriott, H., Nieto, T., O'Grady, J., Olsen, H.E., Pedersen, B.S., Rhie, A., Richardson, H., Quinlan, A.R., Snutch, T.P., Tee, L., Paten, B., Phillippy, A.M., Simpson, J.T., Loman, N.J., and Loose, M.

Abstract

We report the sequencing and assembly of a reference genome for the human GM12878 Utah/Ceph cell line using the MinION (Oxford Nanopore Technologies) nanopore sequencer. 91.2 Gb of sequence data, representing ~30× theoretical coverage, were produced. Reference-based alignment enabled detection of large structural variants and epigenetic modifications. De novo assembly of nanopore reads alone yielded a contiguous assembly (NG50 ~3 Mb). Next, we developed a protocol to generate ultra-long reads (N50 > 100kb, up to 882 kb). Incorporating an additional 5×-coverage of these data more than doubled the assembly contiguity (NG50 ~6.4 Mb). The final assembled genome was 2,867 million bases in size, covering 85.8% of the reference. Assembly accuracy, after incorporating complementary short-read sequencing data, exceeded 99.8%. Ultra-long reads enabled assembly and phasing of the 4 Mb major histocompatibility complex (MHC) locus in its entirety, measurement of telomere repeat length and closure of gaps in the reference human genome assembly GRCh38.

Full Text
View/download PDF

16. Nanopore sequencing and assembly of a human genome with ultra-long reads

Author

Jain, M., Koren, S., Miga, K.H., Quick, J., Rand, A.C., Sasani, T.A., Tyson, J.R., Beggs, A.D., Dilthey, A.T., Fiddes, I.T., Malla, S., Marriott, H., Nieto, T., O'Grady, J., Olsen, H.E., Pedersen, B.S., Rhie, A., Richardson, H., Quinlan, A.R., Snutch, T.P., Tee, L., Paten, B., Phillippy, A.M., Simpson, J.T., Loman, N.J., Loose, M., Jain, M., Koren, S., Miga, K.H., Quick, J., Rand, A.C., Sasani, T.A., Tyson, J.R., Beggs, A.D., Dilthey, A.T., Fiddes, I.T., Malla, S., Marriott, H., Nieto, T., O'Grady, J., Olsen, H.E., Pedersen, B.S., Rhie, A., Richardson, H., Quinlan, A.R., Snutch, T.P., Tee, L., Paten, B., Phillippy, A.M., Simpson, J.T., Loman, N.J., and Loose, M.

Abstract

We report the sequencing and assembly of a reference genome for the human GM12878 Utah/Ceph cell line using the MinION (Oxford Nanopore Technologies) nanopore sequencer. 91.2 Gb of sequence data, representing ~30× theoretical coverage, were produced. Reference-based alignment enabled detection of large structural variants and epigenetic modifications. De novo assembly of nanopore reads alone yielded a contiguous assembly (NG50 ~3 Mb). Next, we developed a protocol to generate ultra-long reads (N50 > 100kb, up to 882 kb). Incorporating an additional 5×-coverage of these data more than doubled the assembly contiguity (NG50 ~6.4 Mb). The final assembled genome was 2,867 million bases in size, covering 85.8% of the reference. Assembly accuracy, after incorporating complementary short-read sequencing data, exceeded 99.8%. Ultra-long reads enabled assembly and phasing of the 4 Mb major histocompatibility complex (MHC) locus in its entirety, measurement of telomere repeat length and closure of gaps in the reference human genome assembly GRCh38.

Full Text
View/download PDF

17. Nanopore sequencing and assembly of a human genome with ultra-long reads

Author

Jain, M., Koren, S., Miga, K.H., Quick, J., Rand, A.C., Sasani, T.A., Tyson, J.R., Beggs, A.D., Dilthey, A.T., Fiddes, I.T., Malla, S., Marriott, H., Nieto, T., O'Grady, J., Olsen, H.E., Pedersen, B.S., Rhie, A., Richardson, H., Quinlan, A.R., Snutch, T.P., Tee, L., Paten, B., Phillippy, A.M., Simpson, J.T., Loman, N.J., Loose, M., Jain, M., Koren, S., Miga, K.H., Quick, J., Rand, A.C., Sasani, T.A., Tyson, J.R., Beggs, A.D., Dilthey, A.T., Fiddes, I.T., Malla, S., Marriott, H., Nieto, T., O'Grady, J., Olsen, H.E., Pedersen, B.S., Rhie, A., Richardson, H., Quinlan, A.R., Snutch, T.P., Tee, L., Paten, B., Phillippy, A.M., Simpson, J.T., Loman, N.J., and Loose, M.

Abstract

We report the sequencing and assembly of a reference genome for the human GM12878 Utah/Ceph cell line using the MinION (Oxford Nanopore Technologies) nanopore sequencer. 91.2 Gb of sequence data, representing ~30× theoretical coverage, were produced. Reference-based alignment enabled detection of large structural variants and epigenetic modifications. De novo assembly of nanopore reads alone yielded a contiguous assembly (NG50 ~3 Mb). Next, we developed a protocol to generate ultra-long reads (N50 > 100kb, up to 882 kb). Incorporating an additional 5×-coverage of these data more than doubled the assembly contiguity (NG50 ~6.4 Mb). The final assembled genome was 2,867 million bases in size, covering 85.8% of the reference. Assembly accuracy, after incorporating complementary short-read sequencing data, exceeded 99.8%. Ultra-long reads enabled assembly and phasing of the 4 Mb major histocompatibility complex (MHC) locus in its entirety, measurement of telomere repeat length and closure of gaps in the reference human genome assembly GRCh38.

Full Text
View/download PDF

18. Nanopore sequencing and assembly of a human genome with ultra-long reads

Author

Jain, M., Koren, S., Miga, K.H., Quick, J., Rand, A.C., Sasani, T.A., Tyson, J.R., Beggs, A.D., Dilthey, A.T., Fiddes, I.T., Malla, S., Marriott, H., Nieto, T., O'Grady, J., Olsen, H.E., Pedersen, B.S., Rhie, A., Richardson, H., Quinlan, A.R., Snutch, T.P., Tee, L., Paten, B., Phillippy, A.M., Simpson, J.T., Loman, N.J., Loose, M., Jain, M., Koren, S., Miga, K.H., Quick, J., Rand, A.C., Sasani, T.A., Tyson, J.R., Beggs, A.D., Dilthey, A.T., Fiddes, I.T., Malla, S., Marriott, H., Nieto, T., O'Grady, J., Olsen, H.E., Pedersen, B.S., Rhie, A., Richardson, H., Quinlan, A.R., Snutch, T.P., Tee, L., Paten, B., Phillippy, A.M., Simpson, J.T., Loman, N.J., and Loose, M.

Abstract

We report the sequencing and assembly of a reference genome for the human GM12878 Utah/Ceph cell line using the MinION (Oxford Nanopore Technologies) nanopore sequencer. 91.2 Gb of sequence data, representing ~30× theoretical coverage, were produced. Reference-based alignment enabled detection of large structural variants and epigenetic modifications. De novo assembly of nanopore reads alone yielded a contiguous assembly (NG50 ~3 Mb). Next, we developed a protocol to generate ultra-long reads (N50 > 100kb, up to 882 kb). Incorporating an additional 5×-coverage of these data more than doubled the assembly contiguity (NG50 ~6.4 Mb). The final assembled genome was 2,867 million bases in size, covering 85.8% of the reference. Assembly accuracy, after incorporating complementary short-read sequencing data, exceeded 99.8%. Ultra-long reads enabled assembly and phasing of the 4 Mb major histocompatibility complex (MHC) locus in its entirety, measurement of telomere repeat length and closure of gaps in the reference human genome assembly GRCh38.

Full Text
View/download PDF

21. Generation of Personalized Donor-Specific Snv Maps from Cfdna in Ex Vivo Lung Perfusate Using Nanopore Sequencing.

Author

Yamamoto, H., Allen, J., Wilson, G.W., Akhter, A., Zuzarte, P.C., Simpson, J.T., Keshavjee, S., and Yeung, J.C.

Subjects
*SHOTGUN sequencing, *CELL-free DNA, *SINGLE nucleotide polymorphisms, *WHOLE genome sequencing, *LUNGS, *DATABASES
Abstract

Donor-derived cell-free DNA (ddcfDNA) has been shown to be useful in monitoring lung graft health. Utilizing nanopore sequencing at relatively low coverage, single nucleotide variant (SNV) differences were identified between donor and recipient genomes in order to distinguish between donor and recipient derived plasma cfDNA. In this study, donor SNVs were called from ex vivo lung perfusion (EVLP) perfusate cfDNA using a Nanopore sequencer and validated by short-read whole genome sequencing (WGS) to verify its accuracy. cfDNA was extracted from 11 clinical EVLP perfusate samples and sequenced using a Nanopore sequencer. SNVs were identified by comparison to a reference genome. Nanopore SNVs were filtered as homozygous calls overlapping 1000Genomes SNP database. Matching short-read whole genome sequencing was performed on 4 matching samples to act as a gold standard. Furthermore, comparing Nanopore's accuracy in detecting ddcfDNA in plasma samples after transplant (Tx) to the WGS library were performed. Nanopore sequencing yielded genomic data with a median coverage of 4.88x using a single flow cell with a median run length of 72h. The median general error rate of the sequence was 5.55%, and the median number of SNP overlap with the 1000 Genomes SNP database was 2469207. When compared to the matching WGS database, the positive predictive value (PPV) of SNVs identified from 4X, 5X, 6X, 7X, and 8X regions were 92%, 95%, 97%, 98%, 98%. (Fig A-D). The nanopore results showed comparable results to the WGS library for ddcfDNA detection in post Tx plasma (Fig E). Despite the lower sequencing accuracy and depth obtained from nanopore sequencing, a high PPV can be achieved in a set of donor-specific SNVs when appropriately filtered by read depth and overlap with SNP databases. This demonstrates potential for the use of nanopore sequencing to generate personalized donor cfDNA maps for use in post-operative donor-derived plasma cfDNA identification. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results