Evidence map›Paper›PMID 33384301›Full record

ArticleScience (New York, N.Y.)2021

In situ genome sequencing resolves DNA sequence and structure in intact biological samples.

Andrew C Payne, Zachary D Chiang, Paul L Reginato, Sarah M Mangiameli, Evan M Murray, Chun-Chen Yao, Styliani Markoulaki, Andrew S Earl, Ajay S Labade, Rudolf Jaenisch and 4 more

Open access · greenAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed
15.6field-weighted citation impact, top 1% 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

124 citing papers in PubMed, 206 citations in OpenAlex.

  1. Article
  2. Review
  3. Insights Into Spatial Transcriptomics: Exploring Recent Technical Developments and Their Diverse Applications.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
  4. Review
  5. Review
  6. Spatially tunable multiomic sequencing using light-driven combinatorial barcoding of molecules in tissues.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review

64 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 1 country.

Andrew C Payne *Media Arts and Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.ORCID https://orcid.org/0000-0002-7212-6994
Zachary D Chiang *Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.ORCID https://orcid.org/0000-0001-6578-2021
Paul L Reginato *Media Arts and Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.ORCID https://orcid.org/0000-0002-7525-9047
Sarah M MangiameliBroad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.ORCID https://orcid.org/0000-0002-6799-3436
Evan M MurrayBroad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Chun-Chen YaoBroad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Styliani MarkoulakiWhitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.ORCID https://orcid.org/0000-0003-4040-2365
Andrew S EarlDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.ORCID https://orcid.org/0000-0002-5732-954X
Ajay S LabadeDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.ORCID https://orcid.org/0000-0003-1348-8220
Rudolf JaenischWhitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.ORCID https://orcid.org/0000-0002-2540-7099
George M ChurchDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.ORCID https://orcid.org/0000-0002-0775-2913
Edward S Boyden *Media Arts and Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. edboyden@mit.edu jason_buenrostro@harvard.edu chenf@broadinstitute.org.ORCID https://orcid.org/0000-0002-0419-3351
Jason D Buenrostro *Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA. edboyden@mit.edu jason_buenrostro@harvard.edu chenf@broadinstitute.org.ORCID https://orcid.org/0000-0001-9958-3987
Fei Chen *Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA. edboyden@mit.edu jason_buenrostro@harvard.edu chenf@broadinstitute.org.ORCID https://orcid.org/0000-0003-2308-3649
Broad Institute · USHarvard University · USHoward Hughes Medical Institute · USIIT@MIT · USWhitehead Institute for Biomedical Research · US

Funding

Tool and Technology Development CoreU19MH114821 · NIMH · COLD SPRING HARBOR LABORATORY · PI HUANG, Z JOSH · 2017 to 2021
$64.5M
Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
Center for Genomically Engineered OrgansRM1HG008525 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2015 to 2019
$10.2M
GENOMIC IMPRINTING AND THE CLONING OF MICER37CA084198 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF · 2000 to 2008
$9.2M
Transcriptional condensates, epigenetic editing and Rett SyndromeR01MH104610 · NIMH · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF, YOUNG, RICHARD · 2014 to 2023
$7.4M
Novel Platforms for Systematic Optical Control of Complex Neural Circuits In VivoR01DA029639 · NIDA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2010 to 2023
$6.7M
Expansion MicroscopyR01EB024261 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2017 to 2025
$4.6M
Millisecond-Timescale Whole-Brain Neural Activity Mapping in Health and DiseaseDP1NS087724 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2013 to 2017
$3.9M
High-Performance Imaging Through Scattering Living TissueR01DA045549 · NIDA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2017 to 2020
$3.5M
An Accessible Optical Toolbox for Saturated Nanoscale Analysis of Neural ArchitectureR01MH110932 · NIMH · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOYDEN, EDWARD S., CAI, DAWEN · 2016 to 2019
$2.8M
Characterizing glioma heterogeneity with novel multiplexed nanoscale imaging technologiesDP5OD024583 · OD · BROAD INSTITUTE, INC. · PI CHEN, FEI · 2017 to 2021
$2.2M
Scalable Cell- and Circuit-Targeted ElectrophysiologyR01NS102727 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S., FOREST, CRAIG · 2017 to 2020
$2.2M
NCI NIH HHS R37 CA084198NHGRI NIH HHS R21 HG009749NHGRI NIH HHS RM1 HG008525NHGRI NIH HHS T32 HG002295NIBIB NIH HHS R01 EB024261NIDA NIH HHS R01 DA029639NIDA NIH HHS R01 DA045549NIH HHS DP5 OD024583NIMH NIH HHS R01 MH104610NIMH NIH HHS R01 MH110932NIMH NIH HHS U19 MH114821NINDS NIH HHS DP1 NS087724NINDS NIH HHS R01 NS087950NINDS NIH HHS R01 NS102727NINDS NIH HHS UF1 NS107697
6 · The paper itself

Abstract

Understanding genome organization requires integration of DNA sequence and three-dimensional spatial context; however, existing genome-wide methods lack either base pair sequence resolution or direct spatial localization. Here, we describe in situ genome sequencing (IGS), a method for simultaneously sequencing and imaging genomes within intact biological samples. We applied IGS to human fibroblasts and early mouse embryos, spatially localizing thousands of genomic loci in individual nuclei. Using these data, we characterized parent-specific changes in genome structure across embryonic stages, revealed single-cell chromatin domains in zygotes, and uncovered epigenetic memory of global chromosome positioning within individual embryos. These results demonstrate how IGS can directly connect sequence and structure across length scales from single base pairs to whole organisms.

Indexed as

GenomeGenome, HumanSequence Analysis, DNAAnimalsBase SequenceCell NucleusChromatinChromosome PositioningChromosomes, HumanChromosomes, MammalianEmbryo, MammalianEmbryonic DevelopmentEpigenesis, GeneticFibroblastsHigh-Throughput Nucleotide SequencingHumansChromatin

Identifiers

PMID33384301
PMCPMC7962746
OpenAlexW3114643239

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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.