Editing Shotgun sequencing (section)

=== Paired-end sequencing ===
Broader application benefited from [[DNA sequencing theory#Pairwise end-sequencing|pairwise end sequencing]], known colloquially as ''double-barrel shotgun sequencing''. As sequencing projects began to take on longer and more complicated DNA sequences, multiple groups began to realize that useful information could be obtained by sequencing both ends of a fragment of DNA. Although sequencing both ends of the same fragment and keeping track of the paired data was more cumbersome than sequencing a single end of two distinct fragments, the knowledge that the two sequences were oriented in opposite directions and were about the length of a fragment apart from each other was valuable in reconstructing the sequence of the original target fragment.

'''History'''. The first published description of the use of paired ends was in 1990<ref>{{cite journal |last1=Edwards |first1=Al |last2=Caskey |first2=C. Thomas |title=Closure strategies for random DNA sequencing |journal=Methods |date=August 1991 |volume=3 |issue=1 |pages=41–47 |doi=10.1016/S1046-2023(05)80162-8}}</ref> as part of the sequencing of the human [[hypoxanthine-guanine phosphoribosyltransferase|HGPRT]] locus, although the use of paired ends was limited to closing gaps after the application of a traditional shotgun sequencing approach. The first theoretical description of a pure pairwise end sequencing strategy, assuming fragments of constant length, was in 1991.<ref>{{cite journal |last1=Edwards |first1=Al |last2=Voss |first2=Hartmut |last3=Rice |first3=Peter |last4=Civitello |first4=Andrew |last5=Stegemann |first5=Josef |last6=Schwager |first6=Christian |last7=Zimmermann |first7=Juergen |last8=Erfle |first8=Holger |last9=Caskey |first9=C.Thomas |last10=Ansorge |first10=Wilhelm |title=Automated DNA sequencing of the human HPRT locus |journal=Genomics |date=April 1990 |volume=6 |issue=4 |pages=593–608 |doi=10.1016/0888-7543(90)90493-E   |pmid=2341149}}</ref> At the time, there was community consensus that the optimal fragment length for pairwise end sequencing would be three times the sequence read length. In 1995 [[Jared Roach|Roach]] et al.<ref>{{cite journal |last1=Roach |first1=Jared C. |last2=Boysen |first2=Cecilie |last3=Wang |first3=Kai |last4=Hood |first4=Leroy |title=Pairwise end sequencing: a unified approach to genomic mapping and sequencing |journal=Genomics |date=March 1995 |volume=26 |issue=2 |pages=345–353 |doi=10.1016/0888-7543(95)80219-C |pmid=7601461}}</ref> introduced the innovation of using fragments of varying sizes, and demonstrated that a pure pairwise end-sequencing strategy would be possible on large targets. The strategy was subsequently adopted by [[The Institute for Genomic Research]] (TIGR) to sequence the genome of the bacterium ''[[Haemophilus influenzae]]'' in 1995,<ref>{{cite journal
  | last = Fleischmann
  | first = RD
  | s2cid = 10423613
 | title = Whole-genome random sequencing and assembly of Haemophilus influenzae Rd
  | journal = Science
  | volume = 269
  | issue = 5223
  | pages = 496–512
  | date = 1995
  | pmid = 7542800
  | doi = 10.1126/science.7542800 |bibcode = 1995Sci...269..496F |display-authors=etal}}</ref> and then by [[Celera Genomics]] to sequence the ''[[Drosophila melanogaster]]'' (fruit fly) genome in 2000,<ref>{{cite journal
 |last            = Adams
 |first           = MD
 |title           = The genome sequence of Drosophila melanogaster
 |journal         = Science
 |volume          = 287
 |issue           = 5461
 |pages           = 2185–95
 |date            = 2000
 |pmid            = 10731132
 |doi             = 10.1126/science.287.5461.2185
 |bibcode         = 2000Sci...287.2185.
 |display-authors = etal
 |url             = http://faculty.evansville.edu/be6/b4456/genomep/adams.pdf
 |citeseerx       = 10.1.1.549.8639
 |access-date     = 2017-10-25
 |archive-date    = 2018-07-22
 |archive-url     = https://web.archive.org/web/20180722001126/http://faculty.evansville.edu/be6/b4456/genomep/adams.pdf
 |url-status      = dead
}}</ref> and subsequently the human genome.