TY  - JOUR
A1  - Marks, Patrick
A1  - Garcia, Sarah
A1  - Barrio, Alvaro Martinez
A1  - Belhocine, Kamila
A1  - Bernate, Jorge
A1  - Bharadwaj, Rajiv
A1  - Bjornson, Keith
A1  - Catalanotti, Claudia
A1  - Delaney, Josh
A1  - Fehr, Adrian
A1  - Fiddes, Ian T.
A1  - Galvin, Brendan
A1  - Heaton, Haynes
A1  - Herschleb, Jill
A1  - Hindson, Christopher
A1  - Holt, Esty
A1  - Jabara, Cassandra B.
A1  - Jett, Susanna
A1  - Keivanfar, Nikka
A1  - Kyriazopoulou-Panagiotopoulou, Sofia
A1  - Lek, Monkol
A1  - Lin, Bill
A1  - Lowe, Adam
A1  - Mahamdallie, Shazia
A1  - Maheshwari, Shamoni
A1  - Makarewicz, Tony
A1  - Marshall, Jamie
A1  - Meschi, Francesca
A1  - O'Keefe, Christopher J.
A1  - Ordonez, Heather
A1  - Patel, Pranav
A1  - Price, Andrew
A1  - Royall, Ariel
A1  - Ruark, Elise
A1  - Seal, Sheila
A1  - Schnall-Levin, Michael
A1  - Shah, Preyas
A1  - Stafford, David
A1  - Williams, Stephen
A1  - Wu, Indira
A1  - Xu, Andrew Wei
A1  - Rahman, Nazneen
A1  - MacArthur, Daniel
A1  - Church, Deanna M.
T1  - Resolving the full spectrum of human genome variation using Linked-Reads
Y1  - 2019/04/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 635 
EP  - 645 
DO  - 10.1101/gr.234443.118 
VL  - 29 
IS  - 4 
UR  - http://genome.cshlp.org/content/29/4/635.abstract 
N2  - Large-scale population analyses coupled with advances in technology have demonstrated that the human genome is more diverse than originally thought. To date, this diversity has largely been uncovered using short-read whole-genome sequencing. However, these short-read approaches fail to give a complete picture of a genome. They struggle to identify structural events, cannot access repetitive regions, and fail to resolve the human genome into haplotypes. Here, we describe an approach that retains long range information while maintaining the advantages of short reads. Starting from ∼1 ng of high molecular weight DNA, we produce barcoded short-read libraries. Novel informatic approaches allow for the barcoded short reads to be associated with their original long molecules producing a novel data type known as “Linked-Reads”. This approach allows for simultaneous detection of small and large variants from a single library. In this manuscript, we show the advantages of Linked-Reads over standard short-read approaches for reference-based analysis. Linked-Reads allow mapping to 38 Mb of sequence not accessible to short reads, adding sequence in 423 difficult-to-sequence genes including disease-relevant genes STRC, SMN1, and SMN2. Both Linked-Read whole-genome and whole-exome sequencing identify complex structural variations, including balanced events and single exon deletions and duplications. Further, Linked-Reads extend the region of high-confidence calls by 68.9 Mb. The data presented here show that Linked-Reads provide a scalable approach for comprehensive genome analysis that is not possible using short reads alone. 
ER  -