Evidence map›Paper›PMID 26067805›Full record

ArticleNature communications2015

Context influences on TALE-DNA binding revealed by quantitative profiling.

Julia M Rogers, Luis A Barrera, Deepak Reyon, Jeffry D Sander, Manolis Kellis, J Keith Joung, Martha L Bulyk

Abstract read
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
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

21 citing papers in PubMed.

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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

7 authors.

Julia M Rogers1] Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA [2] Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, Massachusetts 02138, USA.
Luis A Barrera1] Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA [2] Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, Massachusetts 02138, USA [3] Harvard-MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, Massachusetts 02115, USA [4] Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, Massachusetts 02139, USA.
Deepak Reyon1] Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [2] Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [3] Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [4] Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jeffry D Sander1] Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [2] Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [3] Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [4] Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Manolis KellisComputer Science and Artificial Intelligence Laboratory, MIT, Cambridge, Massachusetts 02139, USA.
J Keith Joung1] Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [2] Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [3] Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [4] Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Martha L Bulyk1] Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA [2] Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, Massachusetts 02138, USA [3] Harvard-MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, Massachusetts 02115, USA [4] Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

Funding

Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
Regulatory Morif Discovery in the Human Genome Using Comparative GenomicsR01HG004037 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS · 2007 to 2015
$3.9M
Advancing stem cell technologies using engineered zinc finger proteinsDP1GM105378 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH · 2012 to 2014
$2.6M
Comparative analysis and regulatory architecture of epigenomics datasetsR01GM113708 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS · 2015 to 2017
$852k
Analysis of TALE-DNA RecognitionR21HG007573 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI BULYK, MARTHA L · 2014 to 2015
$487k
NCCDPHP CDC HHS DP1 GM105378NHGRI NIH HHS R01 HG004037NHGRI NIH HHS R21 HG007573NHGRI NIH HHS T32 HG002295NIGMS NIH HHS DP1 GM105378NIGMS NIH HHS R01 GM113708
6 · The paper itself

Abstract

Transcription activator-like effector (TALE) proteins recognize DNA using a seemingly simple DNA-binding code, which makes them attractive for use in genome engineering technologies that require precise targeting. Although this code is used successfully to design TALEs to target specific sequences, off-target binding has been observed and is difficult to predict. Here we explore TALE-DNA interactions comprehensively by quantitatively assaying the DNA-binding specificities of 21 representative TALEs to ∼5,000-20,000 unique DNA sequences per protein using custom-designed protein-binding microarrays (PBMs). We find that protein context features exert significant influences on binding. Thus, the canonical recognition code does not fully capture the complexity of TALE-DNA binding. We used the PBM data to develop a computational model, Specificity Inference For TAL-Effector Design (SIFTED), to predict the DNA-binding specificity of any TALE. We provide SIFTED as a publicly available web tool that predicts potential genomic off-target sites for improved TALE design.

Indexed as

Base SequenceDNADNA-Binding ProteinsModels, MolecularProtein Array AnalysisProtein BindingDNADNA-Binding Proteins

Identifiers

PMID26067805
PMCPMC4467457

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.