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Record W2985155561 · doi:10.1016/j.cell.2019.10.026

Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing

2019· article· en· W2985155561 on OpenAlexafffund
Emma Laks, Andrew McPherson, Hans Zahn, Daniel Lai, Adi Steif, Jazmine Brimhall, Justina Biele, Beixi Wang, Tehmina Masud, Jerome Ting, Diljot Grewal, Cydney Nielsen, Samantha Leung, Viktoria Bojilova, Maia A. Smith, Oleg Golovko, Steven S.S. Poon, Peter Eirew, Farhia Kabeer, Teresa Ruiz de Algara, So Ra Lee, M. Jafar Taghiyar, Curtis Huebner, Jessica Ngo, Tim Hon Man Chan, Spencer Vatrt-Watts, Pascale Walters, Nafis Abrar, Sophia Chan, Matt Wiens, Lauren Martin, R. Wilder Scott, T. Michael Underhill, Elizabeth A. Chavez, Christian Steidl, Daniel Da Costa, Yussanne Ma, Robin Coope, Richard Corbett, Stephen Pleasance, Richard A. Moore, Andrew J. Mungall, Colin Mar, Fergus Cafferty, Karen A. Gelmon, Stephen Chia, Gregory J. Hannon, Giorgia Battistoni, Dario Bressan, Ian G. Cannell, Hannah Casbolt, Cristina Jauset, Tatjana Kovačević, Claire M. Mulvey, Fiona Nugent, Marta Ribes, Isabella Pearsall, Fatime Qosaj, Kirsty Sawicka, Sophia A. Wild, Elena Williams, Samuel Aparício, Yangguang Li, Ciara H. O’Flanagan, Austin Smith, Teresa Ruíz, Shankar Balasubramanian, Maximillian Lee, Bernd Bodenmiller, Marcel Burger, Laura Kuett, Sandra Tietscher, Jonas Windager, Edward S. Boyden, Shahar Alon, Yi Cui, Amauche Emenari, Dan Goodwin, Emmanouil D. Karagiannis, Anubhav Sinha, Asmamaw T. Wassie, Carlos Caldas, Alejandra Bruna, Maurizio Callari, Wendy Greenwood, Giulia Lerda, Yaniv Lubling, Alastair Marti, Oscar M. Rueda, Abigail Shea, Robby Becker, Flaminia Grimaldi, Suvi Harris, Sara Lisa Vogl, Johanna A. Joyce, Jean Hausser, Spencer S. Watson, Sorhab Shah, Ignacio Vázquez-Garćıa, Simon Tavaré, Khanh N. Dinh, Eyal Fisher, Russell Kunes, Nicolas A. Walton, Mohammad Al Sa’d, Nick Chornay, A. Dariush, Eduardo Gonzales Solares, Carlos González, A. Yoldaş, Neil S. Millar, Xiaowei Zhuang, Jean Fan, Hsuan Lee, Leonardo Sepulveda Duran, Chenglong Xia, Pu Zheng, Marco A. Marra, Carl L. Hansen, Sohrab P. Shah

Bibliographic record

VenueCell · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsBC Cancer AgencyCanada's Michael Smith Genome Sciences CentreGenome British ColumbiaUniversity of British Columbia
FundersNational Cancer InstituteCanadian Cancer Society Research InstituteCanadian Institutes of Health ResearchTerry Fox Research InstituteCancer Research UK
KeywordsBiologyGenomeGeneticsComputational biologySingle-cell analysisOrigin of replicationclone (Java method)Somatic evolution in cancerCellDNAGene

Abstract

fetched live from OpenAlex

Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material. From this resource we have defined variation in mitotic mis-segregation rates across tissue types and genotypes. Analysis of matched genomic and image measurements revealed correlations between cellular morphology and genome ploidy states. Aggregation of cells sharing copy number profiles allowed for calculation of single-nucleotide resolution clonal genotypes and inference of clonal phylogenies and avoided the limitations of bulk deconvolution. Finally, joint analysis over the above features defined clone-specific chromosomal aneuploidy in polyclonal populations.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.006
GPT teacher head0.213
Teacher spread0.206 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations303
Published2019
Admission routes2
Has abstractno

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