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Record W3174638849 · doi:10.1038/s41467-021-23949-5

Single cell derived mRNA signals across human kidney tumors

2021· article· en· W3174638849 on OpenAlexaff
Matthew D. Young, Thomas J. Mitchell, Lars Custers, Thanasis Margaritis, Francisco Morales-Rodriguez, Kwasi Kwakwa, Eleonora Khabirova, Gerda Kildisiute, Thomas R. W. Oliver, Ronald R. de Krijger, Marry M. van den Heuvel‐Eibrink, Federico Comitani, Alice Piapi, Eva Bugallo-Blanco, Christine Thevanesan, Christina Burke, Elena Prigmore, Kirsty Ambridge, Kenny Roberts, Felipe A. Vieira Braga, Tim Coorens, Anna Wilbrey-Clark, Lira Mamanova, Grant D. Stewart, Vincent J. Gnanapragasam, Dyanne Rampling, Neil J. Sebire, Nicholas Coleman, Liz Hook, Anne Y. Warren, Muzlifah Haniffa, Marcel Kool, Stefan M. Pfister, John C. Achermann, Xiaoling He, Roger A. Barker, Adam Shlien, Omer Ali Bayraktar, Sarah A. Teichmann, Frank C. P. Holstege, Kerstin B. Meyer, Jarno Drost, Karin Straathof, Sam Behjati

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsUniversity of TorontoHospital for Sick Children
FundersMedical Research CouncilNational Institute for Health and Care ResearchCancer Research UKWellcome TrustWellcome
KeywordsBiologyCellular differentiationCancerKidneyPathologyGene expressionCellCancer researchGeneMedicineGenetics

Abstract

fetched live from OpenAlex

Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference "cellular signals" in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of "fetalness" with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.

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)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.026
GPT teacher head0.296
Teacher spread0.271 · 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 designObservational
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

Citations59
Published2021
Admission routes1
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicSingle-cell and spatial transcriptomicsFrench-language works237,207