PMID- 28604723
OWN - NLM
STAT- MEDLINE
DCOM- 20170816
LR  - 20240326
IS  - 1548-7105 (Electronic)
IS  - 1548-7091 (Print)
IS  - 1548-7091 (Linking)
VI  - 14
IP  - 7
DP  - 2017 Jul
TI  - FISH-ing for captured contacts: towards reconciling FISH and 3C.
PG  - 673-678
LID - 10.1038/nmeth.4329 [doi]
AB  - Chromosome conformation capture (3C) and fluorescence in situ hybridization 
      (FISH) are two widely used technologies that provide distinct readouts of 3D 
      chromosome organization. While both technologies can assay locus-specific 
      organization, how to integrate views from 3C, or genome-wide Hi-C, and FISH is 
      far from solved. Contact frequency, measured by Hi-C, and spatial distance, 
      measured by FISH, are often assumed to quantify the same phenomena and used 
      interchangeably. Here, however, we demonstrate that contact frequency is distinct 
      from average spatial distance, both in polymer simulations and in experimental 
      data. Performing a systematic analysis of the technologies, we show that this 
      distinction can create a seemingly paradoxical relationship between 3C and FISH, 
      both in minimal polymer models with dynamic looping interactions and in 
      loop-extrusion simulations. Together, our results indicate that cross-validation 
      of Hi-C and FISH should be carefully designed, and that jointly considering 
      contact frequency and spatial distance is crucial for fully understanding 
      chromosome organization.
FAU - Fudenberg, Geoffrey
AU  - Fudenberg G
AD  - Center for the 3D Structure and Physics of the Genome, and Institute for Medical 
      Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, 
      Massachusetts, USA.
FAU - Imakaev, Maxim
AU  - Imakaev M
AD  - Center for the 3D Structure and Physics of the Genome, and Institute for Medical 
      Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, 
      Massachusetts, USA.
LA  - eng
GR  - R01 GM114190/GM/NIGMS NIH HHS/United States
GR  - U54 DK107980/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20170612
PL  - United States
TA  - Nat Methods
JT  - Nature methods
JID - 101215604
SB  - IM
MH  - Animals
MH  - Chromosome Mapping/*methods
MH  - *Chromosomes
MH  - Computer Simulation
MH  - Genetic Techniques
MH  - Genome-Wide Association Study
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Models, Biological
PMC - PMC5517086
MID - NIHMS877402
COIS- Competing interests The authors declare no competing interests exist.
EDAT- 2017/06/13 06:00
MHDA- 2017/08/17 06:00
PMCR- 2017/12/12
CRDT- 2017/06/13 06:00
PHST- 2016/11/14 00:00 [received]
PHST- 2017/05/03 00:00 [accepted]
PHST- 2017/06/13 06:00 [pubmed]
PHST- 2017/08/17 06:00 [medline]
PHST- 2017/06/13 06:00 [entrez]
PHST- 2017/12/12 00:00 [pmc-release]
AID - nmeth.4329 [pii]
AID - 10.1038/nmeth.4329 [doi]
PST - ppublish
SO  - Nat Methods. 2017 Jul;14(7):673-678. doi: 10.1038/nmeth.4329. Epub 2017 Jun 12.