Evidence map›Paper›PMID 27211859›Full record

ArticleCell systems2016

Simultaneous Pathway Activity Inference and Gene Expression Analysis Using RNA Sequencing.

Daniel J O'Connell, Raivo Kolde, Matthew Sooknah, Daniel B Graham, Thomas B Sundberg, Isabel Latorre, Tarjei S Mikkelsen, Ramnik J Xavier

Open access · bronzeAbstract read
In one paragraph

Article in Cell systems, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

29 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
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  5. Scaling perturbations: beyond genome-scale CRISPR screens.bioRxiv : the preprint server for biology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Daniel J O'Connell *Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.
Raivo Kolde *Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Matthew SooknahProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.
Daniel B GrahamProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.
Thomas B SundbergCenter for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142, USA.
Isabel LatorreProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.
Tarjei S MikkelsenBroad Institute, Cambridge, MA 02142, USA.
Ramnik J XavierProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.
Broad Institute · USMassachusetts General Hospital · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Genetic and Pathway Analysis CoreU19AI109725 · NIAID · WASHINGTON UNIVERSITY · PI VIRGIN, HERBERT W · 2014 to 2018
$32.7M
ATG16L1 T300A: genetics to biologyR01DK097485 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI XAVIER, RAMNIK J · 2013 to 2021
$4.1M
NIAID NIH HHS U19 AI109725NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK097485
6 · The paper itself

Abstract

Reporter gene assays are a venerable tool for studying signaling pathways, but they lack the throughput and complexity necessary to contribute to a systems-level understanding of endogenous signaling networks. We present a parallel reporter assay, transcription factor activity sequencing (TF-seq), built on synthetic DNA enhancer elements, which enables parallel measurements in primary cells of the transcriptome and transcription factor activity from more than 40 signaling pathways. Using TF-seq in Myd88(-/-) macrophages, we captured dynamic pathway activity changes underpinning the global transcriptional changes of the innate immune response. We also applied TF-seq to investigate small molecule mechanisms of action and find a role for NF-κB activation and coordination of the STAT1 response in the macrophage reaction to the anti-inflammatory natural product halofuginone. Simultaneous TF-seq and global gene expression profiling represent an integrative approach for gaining mechanistic insight into pathway activity and transcriptional changes that result from genetic and small molecule perturbations.

Indexed as

Sequence Analysis, RNABase SequenceGene Expression ProfilingGene Expression RegulationHigh-Throughput Nucleotide SequencingNF-kappa BRNATranscriptomeNF-kappa BRNA

Identifiers

PMID27211859
PMCPMC5032147
OpenAlexW2397497379

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.