Evidence map›Paper›PMID 28899340›Full record

ArticleBMC genomics2017

Regulatory network changes between cell lines and their tissues of origin.

Camila M Lopes-Ramos, Joseph N Paulson, Cho-Yi Chen, Marieke L Kuijjer, Maud Fagny, John Platig, Abhijeet R Sonawane, Dawn L DeMeo, John Quackenbush, Kimberly Glass

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 84 citations in OpenAlex.

  1. Article
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  9. SMAD5 as a novel gene for familial pulmonary arterial hypertension.Clinical science (London, England : 1979) · 2025
    Article
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  12. AnFrontiers in genetics · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Camila M Lopes-RamosDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Joseph N PaulsonDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Cho-Yi ChenDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Marieke L KuijjerDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Maud FagnyDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
John PlatigDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Abhijeet R SonawaneChanning Division of Network Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Dawn L DeMeoChanning Division of Network Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
John QuackenbushDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA. johnq@jimmy.harvard.edu.
Kimberly GlassDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA. rekrg@channing.harvard.edu.
Dana-Farber Cancer Institute · USHarvard University · USBrigham and Women's Hospital · USCancer Research And Biostatistics · US

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6M
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI BASS, ADAM JOEL · 2007 to 2023
$33.2M
Respiratory Computational Discovery CoreP01HL114501 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHOI, MARY E · 2013 to 2025
$24.9M
SYSTEMS APPROACHES TO THE EPIDEMIOLOGY, GENETICS AND GENOMICS OF LUNG DISEASEST32HL007427 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI DAWN L DEMEO, Edwin K Silverman · 1985 to 2026
$13.6M
Systems Biology, Bioinformatics, and BiostatisticsP01HL105339 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2011 to 2015
$12.2M
Statistical Methods for Analysis of Massive Genetic and Genomic Data in Cancer ResearchR35CA197449 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI XIHONG LIN · 2015 to 2026
$10.9M
Chemical Inhibitors to Define an Essential M. Tuberculosis Signaling NetworkR01AI099204 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI HUSSON, ROBERT N · 2012 to 2016
$6.1M
Using Networks to Assign Gene Function in Lung DiseaseR01HL111759 · NHLBI · DANA-FARBER CANCER INST · PI QUACKENBUSH, JOHN, SILVERMAN, EDWIN K · 2012 to 2015
$3.4M
Genotype and Imaging Phenotype Biomarkers in Lung CancerU01CA190234 · NCI · DANA-FARBER CANCER INST · PI AERTS, HUGO, QUACKENBUSH, JOHN · 2015 to 2019
$3.3M
Using Integrative Networks to Explore Heterogeneous Phenotypes in COPDK25HL133599 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GLASS, KIMBERLY RENEE · 2016 to 2020
$945k
NCI NIH HHS P30 CA006516NCI NIH HHS P50 CA127003NCI NIH HHS R35 CA197449NCI NIH HHS U01 CA190234NHLBI NIH HHS K25 HL133599NHLBI NIH HHS P01 HL105339NHLBI NIH HHS P01 HL114501NHLBI NIH HHS R01 HL111759NIAID NIH HHS R01 AI099204
6 · The paper itself

Abstract

backgroundCell lines are an indispensable tool in biomedical research and often used as surrogates for tissues. Although there are recognized important cellular and transcriptomic differences between cell lines and tissues, a systematic overview of the differences between the regulatory processes of a cell line and those of its tissue of origin has not been conducted. The RNA-Seq data generated by the GTEx project is the first available data resource in which it is possible to perform a large-scale transcriptional and regulatory network analysis comparing cell lines with their tissues of origin.

resultsWe compared 127 paired Epstein-Barr virus transformed lymphoblastoid cell lines (LCLs) and whole blood samples, and 244 paired primary fibroblast cell lines and skin samples. While gene expression analysis confirms that these cell lines carry the expression signatures of their primary tissues, albeit at reduced levels, network analysis indicates that expression changes are the cumulative result of many previously unreported alterations in transcription factor (TF) regulation. More specifically, cell cycle genes are over-expressed in cell lines compared to primary tissues, and this alteration in expression is a result of less repressive TF targeting. We confirmed these regulatory changes for four TFs, including SMAD5, using independent ChIP-seq data from ENCODE.

conclusionsOur results provide novel insights into the regulatory mechanisms controlling the expression differences between cell lines and tissues. The strong changes in TF regulation that we observe suggest that network changes, in addition to transcriptional levels, should be considered when using cell lines as models for tissues.

Indexed as

Gene Expression ProfilingGene Regulatory NetworksCell CycleCell LineHumansOrgan SpecificityFibroblast cell linesGTExLymphoblastoid cell linesRegulatory networksTranscriptome

Identifiers

PMID28899340
PMCPMC5596945
OpenAlexW2754808057

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.