PMID- 28714986
OWN - NLM
STAT- MEDLINE
DCOM- 20170925
LR  - 20181113
IS  - 1548-7105 (Electronic)
IS  - 1548-7091 (Print)
IS  - 1548-7091 (Linking)
VI  - 14
IP  - 9
DP  - 2017 Sep
TI  - Genome-wide reconstruction of complex structural variants using read clouds.
PG  - 915-920
LID - 10.1038/nmeth.4366 [doi]
AB  - In read cloud approaches, microfluidic partitioning of long genomic DNA fragments 
      and barcoding of shorter fragments derived from these fragments retains 
      long-range information in short sequencing reads. This combination of short reads 
      with long-range information represents a powerful alternative to single-molecule 
      long-read sequencing. We develop Genome-wide Reconstruction of Complex Structural 
      Variants (GROC-SVs) for SV detection and assembly from read cloud data and apply 
      this method to Illumina-sequenced 10x Genomics sarcoma and breast cancer data 
      sets. Compared with short-fragment sequencing, GROC-SVs substantially improves 
      the specificity of breakpoint detection at comparable sensitivity. This approach 
      also performs sequence assembly across multiple breakpoints simultaneously, 
      enabling the reconstruction of events exhibiting remarkable complexity. We show 
      that chromothriptic rearrangements occurred before copy number amplifications, 
      and that rates of single-nucleotide variants and SVs are not correlated. Our 
      results support the use of read cloud approaches to advance the characterization 
      of large and complex structural variation.
FAU - Spies, Noah
AU  - Spies N
AUID- ORCID: 0000-0002-6759-9842
AD  - Genome-scale Measurements Group, National Institute of Standards and Technology, 
      Gaithersburg, Maryland, USA.
AD  - Joint Initiative for Metrology in Biology, Stanford, California, USA.
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, 
      California, USA.
FAU - Weng, Ziming
AU  - Weng Z
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, 
      California, USA.
FAU - Bishara, Alex
AU  - Bishara A
AD  - Department of Computer Science, Stanford University, Stanford, California, USA.
FAU - McDaniel, Jennifer
AU  - McDaniel J
AD  - Genome-scale Measurements Group, National Institute of Standards and Technology, 
      Gaithersburg, Maryland, USA.
FAU - Catoe, David
AU  - Catoe D
AD  - Genome-scale Measurements Group, National Institute of Standards and Technology, 
      Gaithersburg, Maryland, USA.
FAU - Zook, Justin M
AU  - Zook JM
AD  - Genome-scale Measurements Group, National Institute of Standards and Technology, 
      Gaithersburg, Maryland, USA.
FAU - Salit, Marc
AU  - Salit M
AD  - Genome-scale Measurements Group, National Institute of Standards and Technology, 
      Gaithersburg, Maryland, USA.
AD  - Joint Initiative for Metrology in Biology, Stanford, California, USA.
FAU - West, Robert B
AU  - West RB
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, 
      California, USA.
FAU - Batzoglou, Serafim
AU  - Batzoglou S
AD  - Department of Computer Science, Stanford University, Stanford, California, USA.
FAU - Sidow, Arend
AU  - Sidow A
AUID- ORCID: 0000-0002-8287-331X
AD  - Joint Initiative for Metrology in Biology, Stanford, California, USA.
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, 
      California, USA.
AD  - Department of Genetics, Stanford University School of Medicine, Stanford, 
      California, USA.
LA  - eng
GR  - R01 CA183904/CA/NCI NIH HHS/United States
GR  - T32 HG000044/HG/NHGRI NIH HHS/United States
PT  - Journal Article
DEP - 20170717
PL  - United States
TA  - Nat Methods
JT  - Nature methods
JID - 101215604
SB  - IM
MH  - *Algorithms
MH  - Chromosome Mapping/*methods
MH  - DNA Mutational Analysis/*methods
MH  - Genetic Variation/*genetics
MH  - Genome/*genetics
MH  - High-Throughput Nucleotide Sequencing/*methods
MH  - Sequence Analysis, DNA/*methods
PMC - PMC5578891
MID - NIHMS887914
COIS- Competing Financial Interests Statement The authors declare no competing 
      financial interests.
EDAT- 2017/07/18 06:00
MHDA- 2017/09/26 06:00
PMCR- 2018/01/17
CRDT- 2017/07/18 06:00
PHST- 2016/11/07 00:00 [received]
PHST- 2017/06/15 00:00 [accepted]
PHST- 2017/07/18 06:00 [pubmed]
PHST- 2017/09/26 06:00 [medline]
PHST- 2017/07/18 06:00 [entrez]
PHST- 2018/01/17 00:00 [pmc-release]
AID - nmeth.4366 [pii]
AID - 10.1038/nmeth.4366 [doi]
PST - ppublish
SO  - Nat Methods. 2017 Sep;14(9):915-920. doi: 10.1038/nmeth.4366. Epub 2017 Jul 17.