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Record W2007771322 · doi:10.1038/ng.375

The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line

2009· article· en· W2007771322 on OpenAlexaff
Hideya Kawaji, Norihiro Maeda, Takehiro Hashimoto, Kayoko Murakami, Andreas Lennartsson, Timo Lassmann, Kazumi Yamaguchi, Shohei Noma, Yayoi Kitazume, Noriko Ninomiya, Yasuhiro Tomaru, Ryoko Ishihara, Chika Kawazu, Shiro Fukuda, Nicolas Bertin, Takahiro Suzuki, Mika Nakano, Chikatoshi Kai, Tsugumi Kawashima, Y. Hayashizaki, Chihiro Ogawa, Yuki Hasegawa, Carsten O. Daub, Jessica Severin, Takuma Sano, Kazunori Waki, Mutsumi Kanamori-Katayama, Harukazu Suzuki, Shintaro Katayama, Yukari Takahashi, Hiromi Nishiyori, Masaaki Furuno, Andrew Waterhouse, Haruka Okuda-Yabukami, Miki Kojima, Charles Plessy, Erika Bulger, Erik Arner, Shinji Kondo, Mitsuyoshi Murata, Michihira Tagami, Michiel de Hoon, Yoshinari Ando, Jun Yasuda, Hisashi Miura, Atsutaka Kubosaki, Piero Carninci, Christophe Simon, Jun Kawai, Kengo Imamura, Masanori Suzuki, Takahiro Arakawa, Yasumasa Kimura, Marina Lizio, Ai Kaiho, Christine A. Wells, Alistair M. Chalk, Anthony G Beckhouse, Nicholas Matigian, Piotr J. Balwierz, Mihaela Zavolan, Erik van Nimwegen, Mikhail Pachkov, Katharine M. Irvine, Kate Schroder, Timothy L. Bailey, Denis C. Bauer, Timothy Ravasi, Ariel Schwartz, Kai Tan, Altuna Akalin, Pär G. Engström, Boris Lenhard, David Fredman, Megumi Hashimoto, Maki Asada, Hiroshi Asahara, Magbubah Essack, Adam Dawe, Vladimir B. Bajić, Adéle Kruger, Aleksandar Radovanović, Mandeep Kaur, Cameron Ross MacPherson, Monique Maqungo, Christopher A. Maher, Stuart Meier, Sebastian Schmeier, Johan Björkegren, Jesper Tegnér, Frank Brombacher, Joe Chiba, Kazuhiko Nakabayashi, Ryuichiro Kimura, Ryan J. Taft, Sean M. Grimmond, John S. Mattick, Geoffrey J. Faulkner, Cas Simons, Nicole Cloonan, Josée Dostie, J. Lynn Fink, Markus C. Kerr, Rohan D. Teasdale, Ko Fujimori, T. Konno, Takashi Gojobori, Toshitsugu Okayama, Sei Miyamoto, Miho Sera, Kazuho Ikeo, Julian Gough, Michael Hörnquist, Mika Gustafsson, Mariko Hatakeyama, Toshio Kojima, Linda Wu, Susanne Heinzel, Nikolai Petrovsky, Łukasz Huminiecki, Naoko Imamoto, Satoshi Inoue, Yusuke Inoue, Takao Iwayanagi, Albin Sandelin, Ole Winther, Sanne Nygaard, Anders Krogh, Eivind Valen, Morten Lindow, Syuhei Kimura, Hiroaki Kitano, Hisashi Koga, George St. Laurent, Ajit Kumar, Jessica C. Mar, John Quackenbush, Yoichi Takenaka, Hideo Matsuda, Hiroshi Yanagawa, Etsuko Miyamoto‐Sato, Yutaka Nakachi, Yasushi Okazaki, Valerio Orlando, Jun Otomo, Shizu Takeda, Michael Rehli, Rintaro Saito, Christian Schönbach, Colin A. Semple, Katsuhiko Shirahige, Matthew J. Sweet, Martin S. Taylor

Bibliographic record

VenueNature Genetics · 2009
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Chromatin Dynamics
Canadian institutionsMcGill University
FundersU.S. National Library of MedicineMedical Research CouncilNational Heart, Lung, and Blood InstituteSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungMinistry of Education, Culture, Sports, Science and TechnologyRIKENNational Health and Medical Research CouncilWellcome Trust
KeywordsBiologyTranscription factorGene knockdownCellular differentiationGene regulatory networkTranscription (linguistics)Transcriptional regulationCell biologyMyeloid leukemiaRegulation of gene expressionComputational biologyCell cultureGeneGeneticsGene expressionCancer research

Abstract

fetched live from OpenAlex

The FANTOM4 study identified transcriptional start sites active during proliferation arrest and differentiation of the human monocytic cell line THP-1. Systematic knockdown of 52 transcription factors provide support for their model in which a complex transcriptional network regulates the differentiation process. Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
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 head0.004
GPT teacher head0.207
Teacher spread0.203 · 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

Citations430
Published2009
Admission routes1
Has abstractno

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