IP Library › Granted Patent US 12,365,933
Granted Patent B2
US 12,365,933 · App. 18/329,431 · Granted Jul 22, 2025

Systems and methods for epigenetic analysis

Inventors: Devin Locke (Medford, MA); Wan-Ping Lee (Somerville, MA)
Assignee: Seven Bridges Genomics Inc.
C12Q1/6806C12Q1/6869C12Q1/6874G16B30/00G16B30/10
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,365,933
App. No.
18/329,431
Granted
Jul 22, 2025
Kind
B2
Abstract

The invention provides systems and methods for determining patterns of modification to a genome of a subject by representing the genome using a graph, such as a directed acyclic graph (DAG) with divergent paths for regions that are potentially subject to modification, profiling segments of the genome for evidence of epigenetic modification, and aligning the profiled segments to the DAG to determine locations and patterns of the epigenetic modification within the genome.

Claims (66)

1. A method for determining epigenetic modifications in a first sequence of nucleotide bases representing at least a portion of a genome of a subject, the first sequence having been previously-obtained by sequencing nucleic acid from the subject, the method comprising:

using at least one processor to perform:

accessing a graph stored in at least one non-transitory memory, the graph representing, at each of a plurality of positions in the graph, a respective cytosine base of a plurality of cytosine bases in the first sequence and a respective thymine base of a plurality of thymine bases not in the first sequence, the graph comprising nodes and edges stored as objects in the at least one non-transitory memory, at least some of the objects including respective pointers to other objects representing other nodes, the nodes including:

a first node representing a cytosine base of the plurality of cytosine bases at a position of the plurality of positions, wherein the first node is stored as a first object in the at least one non-transitory memory, the first object comprising a first list of one or more pointers stored in the at least one non-transitory memory, and

a second node representing a thymine base of the plurality of thymine bases at the position, wherein the second node is stored as a second object in the at least one non-transitory memory, the second object comprising a second list of one or more pointers stored in the at least one non-transitory memory; and

aligning a second sequence of nucleotide bases to the graph to determine a proportion of a number of methylated cytosine bases to a total number of cytosine bases in at least the portion of the subject's genome, the second sequence representing at least the portion of the subject's genome and having been previously-obtained by sequencing bisulfite-treated nucleic acid from the subject, and the aligning comprising aligning the second sequence of nucleotide bases to the graph using (i) the objects including the first object and the second object, and (ii) the pointers including the first list of one or more pointers and the second list of one or more pointers.

2. The method of claim 1 , further comprising determining the total number of cytosine bases in at least the portion of the subject's genome, the determining comprising:

determining a number of the plurality of cytosine bases in the first sequence.

3. The method of claim 2 , wherein:

the second sequence comprises thymine bases,

aligning the second sequence to the graph comprises aligning each of at least some of the thymine bases in the second sequence to a respective thymine base of the plurality of thymine bases not in the first sequence, and

the method further comprises determining the number of methylated cytosine bases in at least the portion of the subject's genome at least in part by determining a number of the at least some of the thymine bases in the second sequence.

4. The method of claim 1 , further comprising:

determining, based on the determined proportion of the number of methylated cytosine bases to the total number of cytosine bases in at least the portion of the subject's genome, whether transcription of a gene in the subject's genome has been regulated.

5. The method of claim 1 , further comprising creating the graph in the at least one non-transitory memory using the first sequence, the creating comprising:

creating a first subset of the nodes of the graph, the first subset of the nodes including the first node and representing the first sequence; and

creating a second subset of the nodes of the graph, the second subset of the nodes including the second node and representing the plurality of thymine bases not included in the first sequence.

6. The method of claim 1 , further comprising:

identifying one or more variants in the first sequence of nucleotide bases.

7. The method of claim 1 , wherein the portion of the subject's genome is at least 50% of a length of a chromosome of the subject's genome.

8. The method of claim 1 , further comprising:

treating the nucleic acid from the subject with bisulfite to obtain the bisulfite-treated nucleic acid; and

sequencing the bisulfite-treated nucleic acid.

9. A system, comprising:

at least one processor; and

at least one non-transitory memory storing processor-executable instructions that, when executed by the at least one processor, cause the at least one processor to perform a method for determining epigenetic modifications in a first sequence of nucleotide bases representing at least a portion of a genome of a subject, the first sequence having been previously-obtained by sequencing nucleic acid from the subject, the method comprising:

accessing a graph stored in the at least one non-transitory memory, the graph representing, at each of a plurality of positions in the graph, a respective cytosine base of a plurality of cytosine bases in the first sequence and a respective thymine base of a plurality of thymine bases not in the first sequence, the graph comprising nodes and edges stored as objects in the at least one non-transitory memory, at least some of the objects including respective pointers to other objects representing other nodes, the nodes including:

a first node representing a cytosine base of the plurality of cytosine bases at a position of the plurality of positions, wherein the first node is stored as a first object in the at least one non-transitory memory, the first object comprising a first list of one or more pointers stored in the at least one non-transitory memory, and

a second node representing a thymine base of the plurality of thymine bases at the position, wherein the second node is stored as a second object in the at least one non-transitory memory, the second object comprising a second list of one or more pointers stored in the at least one non-transitory memory; and

aligning a second sequence of nucleotide bases to the graph to determine a proportion of a number of methylated cytosine bases to a total number of cytosine bases in at least the portion of the subject's genome, the second sequence representing at least the portion of the subject's genome and having been previously-obtained by sequencing bisulfite-treated nucleic acid from the subject, and the aligning comprising aligning the second sequence of nucleotide bases to the graph using (i) the objects including the first object and the second object, and (ii) the pointers including the first list of one or more pointers and the second list of one or more pointers.

10. The system of claim 9 , further comprising:

determining, based on the determined proportion of the number of methylated cytosine bases to the total number of cytosine bases in at least the portion of the subject's genome, whether transcription of a gene in the subject's genome has been regulated.

11. The system of claim 9 , further comprising creating the graph in the at least one non-transitory memory using the first sequence, the creating comprising:

creating a first subset of the nodes of the graph, the first subset of the nodes including the first node and representing the first sequence; and

creating a second subset of the nodes of the graph, the second subset of the nodes including the second node and representing the plurality of thymine bases not included in the first sequence.

12. The system of claim 9 , wherein the portion of the subject's genome is at least 50% of a length of a chromosome of the subject's genome.

13. The system of claim 9 , further comprising:

treating the nucleic acid from the subject with bisulfite to obtain the bisulfite-treated nucleic acid; and

sequencing the bisulfite-treated nucleic acid.

14. At least one non-transitory memory storing processor-executable instructions that, when executed by at least one processor, cause the at least one processor to perform a method for determining epigenetic modifications in a first sequence of nucleotide bases representing at least a portion of a genome of a subject, the first sequence having been previously-obtained by sequencing nucleic acid from the subject, the method comprising:

accessing a graph stored in the at least one non-transitory memory, the graph representing, at each of a plurality of positions in the graph, a respective cytosine base of a plurality of cytosine bases in the first sequence and a respective thymine base of a plurality of thymine bases not in the first sequence, the graph comprising nodes and edges stored as objects in the at least one non-transitory memory, at least some of the objects including respective pointers to other objects representing other nodes, the nodes including:

a first node representing a cytosine base of the plurality of cytosine bases at a position of the plurality of positions, wherein the first node is stored as a first object in the at least one non-transitory memory, the first object comprising a first list of one or more pointers stored in the at least one non-transitory memory, and

a second node representing a thymine base of the plurality of thymine bases at the position, wherein the second node is stored as a second object in the at least one non-transitory memory, the second object comprising a second list of one or more pointers stored in the at least one non-transitory memory; and

aligning a second sequence of nucleotide bases to the graph to determine a proportion of a number of methylated cytosine bases to a total number of cytosine bases in at least the portion of the subject's genome, the second sequence representing at least the portion of the subject's genome and having been previously-obtained by sequencing bisulfite-treated nucleic acid from the subject, and the aligning comprising aligning the second sequence of nucleotide bases to the graph using (i) the objects including the first object and the second object, and (ii) the pointers including the first list of one or more pointers and the second list of one or more pointers.

15. The at least one non-transitory memory of claim 14 , further comprising:

determining, based on the determined proportion of the number of methylated cytosine bases to the total number of cytosine bases in at least the portion of the subject's genome, whether transcription of a gene in the subject's genome has been regulated.

16. The at least one non-transitory memory of claim 14 , further comprising creating the graph in the at least one non-transitory memory using the first sequence, the creating comprising:

creating a first subset of the nodes of the graph, the first subset of the nodes including the first node and representing the first sequence; and

creating a second subset of the nodes of the graph, the second subset of the nodes including the second node and representing the plurality of thymine bases not included in the first sequence.

17. The at least one non-transitory memory of claim 14 , further comprising:

treating at least a portion of the nucleic acid from the subject with bisulfite to obtain the bisulfite-treated nucleic acid; and

sequencing the bisulfite-treated nucleic acid.

18. A method for determining epigenetic modifications, the method comprising:

obtaining a nucleic acid previously obtained from a subject;

sequencing the nucleic acid to obtain a first sequence of nucleotide bases representing at least a portion of a genome of the subject;

creating a graph in at least one non-transitory memory using the first sequence, the graph representing, at each of a plurality of positions in the graph, a respective cytosine base of a plurality of cytosine bases in the first sequence and a respective thymine base of a plurality of thymine bases not in the first sequence, wherein creating the graph comprises storing objects in the at least one non-transitory memory, the objects representing nodes and edges connecting the nodes, at least some of the objects including respective pointers to other objects representing other nodes, the nodes including:

a first node representing a cytosine base of the plurality of cytosine bases at a position of the plurality of positions, wherein the first node is stored as a first object in the at least one non-transitory memory, the first object comprising a first list of one or more pointers stored in the at least one non-transitory memory, and

a second node representing a thymine base of the plurality of thymine bases at the position, wherein the second node is stored as a second object in the at least one non-transitory memory, the second object comprising a second list of one or more pointers stored in the at least one non-transitory memory;

treating the nucleic acid with bisulfite to obtain a bisulfite-treated nucleic acid;

sequencing the bisulfite-treated nucleic acid to obtain a second sequence of nucleotide bases; and

aligning the second sequence of nucleotide bases to the graph using (i) the objects including the first object and the second object, and (ii) the pointers including the first list of one or more pointers and the second list of one or more pointers.

19. The method of claim 18 , further comprising:

identifying, based on a result of aligning the second sequence of nucleotide bases to the graph, a presence of at least one methylated cytosine in at least the portion of the subject's genome; and

generating an output indicating the presence of the at least one methylated cytosine in at least the portion of the subject's genome.

20. The method of claim 18 , further comprising:

determining, based on a result of aligning the second sequence of nucleotide bases to the graph, a proportion of a number of methylated cytosine bases to a total number of cytosine bases in at least the portion of the subject's genome.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 25, 2023
From: LOCKE, DEVIN; LEE, WAN-PING
To: SEVEN BRIDGES GENOMICS INC.
Reel/Frame 065007/0237 →
SECURITY INTEREST Recorded Jul 31, 2023
From: SEVEN BRIDGES GENOMICS INC.
To: ORBIMED ROYALTY & CREDIT OPPORTUNITIES III, LP
Reel/Frame 064431/0327 →
Continuity (4)
Continuation 17023289 · Sep 16, 2020
Continuation 15007874 · Jan 27, 2016
Provisional Application 62209058 · Aug 24, 2015
Related Publication 20240011074A1 · Jan 11, 2024
References Cited (400)
US 4683195A · Mullis et al. · 1987 [cited by applicant]
US 4683202A · Mullis · 1987 [cited by applicant]
US 4988617A · Landegren et al. · 1991 [cited by applicant]
US 5234809A · Boom et al. · 1993 [cited by applicant]
US 5242794A · Whiteley et al. · 1993 [cited by applicant]
US 5494810A · Barany et al. · 1996 [cited by applicant]
US 5511158A · Sims · 1996 [cited by applicant]
US 5583024A · McElroy et al. · 1996 [cited by applicant]
US 5674713A · McElroy et al. · 1997 [cited by applicant]
US 5700673A · McElroy et al. · 1997 [cited by applicant]
US 5701256A · Marr et al. · 1997 [cited by applicant]
US 6054278A · Dodge et al. · 2000 [cited by applicant]
US 6210891B1 · Nyren et al. · 2001 [cited by applicant]
US 6223128B1 · Allex et al. · 2001 [cited by applicant]
US 6306597B1 · Macevicz · 2001 [cited by applicant]
US 6582938B1 · Su et al. · 2003 [cited by applicant]
US 6818395B1 · Quake et al. · 2004 [cited by applicant]
US 6828100B1 · Ronaghi · 2004 [cited by applicant]
US 6833246B2 · Balasubramanian · 2004 [cited by applicant]
US 6890763B2 · Jackowski et al. · 2005 [cited by applicant]
US 6911345B2 · Quake et al. · 2005 [cited by applicant]
US 6925389B2 · Hitt et al. · 2005 [cited by applicant]
US 6989100B2 · Norton · 2006 [cited by applicant]
US 7169560B2 · Lapidus et al. · 2007 [cited by applicant]
US 7232656B2 · Balasubramanian et al. · 2007 [cited by applicant]
US 7282337B1 · Harris · 2007 [cited by applicant]
US 7321623B2 · Dambrackas · 2008 [cited by applicant]
US 7483585B2 · Brakus, Jr. · 2009 [cited by applicant]
US 7577554B2 · Lystad et al. · 2009 [cited by applicant]
US 7580918B2 · Chang et al. · 2009 [cited by applicant]
US 7598035B2 · Macevicz · 2009 [cited by applicant]
US 7620800B2 · Huppenthal et al. · 2009 [cited by applicant]
US 7776616B2 · Heath et al. · 2010 [cited by applicant]
US 7809509B2 · Milosavljevic · 2010 [cited by applicant]
US 7835871B2 · Kain et al. · 2010 [cited by applicant]
US 7885840B2 · Sadiq et al. · 2011 [cited by applicant]
US 7917302B2 · Rognes · 2011 [cited by applicant]
US 7957913B2 · Chinitz et al. · 2011 [cited by applicant]
US 7960120B2 · Rigatti et al. · 2011 [cited by applicant]
US 8146099B2 · Tkatch et al. · 2012 [cited by applicant]
US 8165821B2 · Zhang · 2012 [cited by applicant]
US 8209130B1 · Kennedy et al. · 2012 [cited by applicant]
US 8340914B2 · Gatewood et al. · 2012 [cited by applicant]
US 8370079B2 · Sorenson et al. · 2013 [cited by applicant]
US 8639847B2 · Blaszczak et al. · 2014 [cited by applicant]
US 8972201B2 · Mande et al. · 2015 [cited by applicant]
US 9063914B2 · Kural et al. · 2015 [cited by applicant]
US 9092402B2 · Kural et al. · 2015 [cited by applicant]
US 9116866B2 · Kural · 2015 [cited by applicant]
US 9390226B2 · Kural · 2016 [cited by applicant]
US 9817944B2 · Kural · 2017 [cited by applicant]
US 10584380B2 · Locke et al. · 2020 [cited by applicant]
US 10724110B2 · Locke et al. · 2020 [cited by applicant]
US 10793895B2 · Locke et al. · 2020 [cited by applicant]
US 11649495B2 · Locke et al. · 2023 [cited by applicant]
US 11697835B2 · Locke et al. · 2023 [cited by applicant]
US 11702708B2 · Locke et al. · 2023 [cited by applicant]
US 20020164629A1 · Quake et al. · 2002 [cited by applicant]
US 20020190663A1 · Rasmussen · 2002 [cited by applicant]
US 20030032026A1 · Berlin · 2003 [cited by applicant]
US 20040023209A1 · Jonasson · 2004 [cited by applicant]
US 20050089906A1 · Furuta et al. · 2005 [cited by applicant]
US 20060024681A1 · Smith et al. · 2006 [cited by applicant]
US 20060195269A1 · Yeatman et al. · 2006 [cited by applicant]
US 20060292611A1 · Berka et al. · 2006 [cited by applicant]
US 20070087365A1 · Van Criekinge et al. · 2007 [cited by applicant]
US 20070114362A1 · Feng et al. · 2007 [cited by applicant]
US 20070166707A1 · Schadt et al. · 2007 [cited by applicant]
US 20070218467A1 · Ecker et al. · 2007 [cited by applicant]
US 20080003571A1 · McKernan et al. · 2008 [cited by applicant]
US 20080077607A1 · Gatawood et al. · 2008 [cited by applicant]
US 20080251711A1 · Reilly · 2008 [cited by applicant]
US 20080281463A1 · Suh et al. · 2008 [cited by applicant]
US 20080294403A1 · Zhu et al. · 2008 [cited by applicant]
US 20090026082A1 · Rothberg et al. · 2009 [cited by applicant]
US 20090119313A1 · Pearce · 2009 [cited by applicant]
US 20090127589A1 · Rothberg et al. · 2009 [cited by applicant]
US 20090164135A1 · Brodzik et al. · 2009 [cited by applicant]
US 20090191565A1 · Lapidus et al. · 2009 [cited by applicant]
US 20090233809A1 · Faham et al. · 2009 [cited by applicant]
US 20090300781A1 · Bancroft et al. · 2009 [cited by applicant]
US 20090318310A1 · Liu et al. · 2009 [cited by applicant]
US 20090325145A1 · Sablon et al. · 2009 [cited by applicant]
US 20100010992A1 · Morris · 2010 [cited by applicant]
US 20100035252A1 · Rothberg et al. · 2010 [cited by applicant]
US 20100041048A1 · Diehi et al. · 2010 [cited by applicant]
US 20100137143A1 · Rothberg et al. · 2010 [cited by applicant]
US 20100169026A1 · Sorenson et al. · 2010 [cited by applicant]
US 20100188073A1 · Rothberg et al. · 2010 [cited by applicant]
US 20100197507A1 · Rothberg et al. · 2010 [cited by applicant]
US 20100240046A1 · Palmer et al. · 2010 [cited by applicant]
US 20100282617A1 · Rothberg et al. · 2010 [cited by applicant]
US 20100285578A1 · Selden et al. · 2010 [cited by applicant]
US 20100300559A1 · Schultz et al. · 2010 [cited by applicant]
US 20100300895A1 · Nobile et al. · 2010 [cited by applicant]
US 20100301398A1 · Rothberg et al. · 2010 [cited by applicant]
US 20100304982A1 · Hinz et al. · 2010 [cited by applicant]
US 20110004413A1 · Carnevali et al. · 2011 [cited by applicant]
US 20110009278A1 · Kain et al. · 2011 [cited by applicant]
US 20110098193A1 · Kingsmore et al. · 2011 [cited by applicant]
US 20110207135A1 · Faham et al. · 2011 [cited by applicant]
US 20110257889A1 · Klammer et al. · 2011 [cited by applicant]
US 20120030566A1 · Victor · 2012 [cited by applicant]
US 20120040851A1 · Lieberman et al. · 2012 [cited by applicant]
US 20120041727A1 · Mishra et al. · 2012 [cited by applicant]
US 20120045771A1 · Beier et al. · 2012 [cited by applicant]
US 20120157322A1 · Myllykangas et al. · 2012 [cited by applicant]
US 20120239706A1 · Steinfadt · 2012 [cited by applicant]
US 20120330566A1 · Chaisson · 2012 [cited by applicant]
US 20130029879A1 · Shelly et al. · 2013 [cited by applicant]
US 20130035904A1 · Kuhn · 2013 [cited by applicant]
US 20130059738A1 · Leamon et al. · 2013 [cited by applicant]
US 20130059740A1 · Drmanac et al. · 2013 [cited by applicant]
US 20130073214A1 · Hyland et al. · 2013 [cited by applicant]
US 20130124100A1 · Drmanac et al. · 2013 [cited by applicant]
US 20130138358A1 · Tang et al. · 2013 [cited by applicant]
US 20130232480A1 · Winterfeldt et al. · 2013 [cited by applicant]
US 20130289099A1 · Le Goff et al. · 2013 [cited by applicant]
US 20130311106A1 · White et al. · 2013 [cited by applicant]
US 20130332081A1 · Reese et al. · 2013 [cited by applicant]
US 20130345066A1 · Brinza et al. · 2013 [cited by applicant]
US 20140012866A1 · Bowman et al. · 2014 [cited by applicant]
US 20140025312A1 · Chin et al. · 2014 [cited by applicant]
US 20140051588A9 · Drmanac et al. · 2014 [cited by applicant]
US 20140066317A1 · Talasaz · 2014 [cited by applicant]
US 20140129201A1 · Kennedy et al. · 2014 [cited by applicant]
US 20140136120A1 · Colwell et al. · 2014 [cited by applicant]
US 20140195564A1 · Talagala et al. · 2014 [cited by applicant]
US 20140200147A1 · Bartha et al. · 2014 [cited by applicant]
US 20140278590A1 · Abbassi et al. · 2014 [cited by applicant]
US 20140280360A1 · Webber et al. · 2014 [cited by applicant]
US 20140281708A1 · Adam et al. · 2014 [cited by applicant]
US 20140323320A1 · Jia et al. · 2014 [cited by applicant]
US 20140371110A1 · Van Rooyen et al. · 2014 [cited by applicant]
US 20150020061A1 · Ravi · 2015 [cited by applicant]
US 20150056613A1 · Kural · 2015 [cited by applicant]
US 20150057946A1 · Kural · 2015 [cited by applicant]
US 20150066383A1 · Wernicke · 2015 [cited by applicant]
US 20150094212A1 · Gottimukkala et al. · 2015 [cited by applicant]
US 20150110754A1 · Bai et al. · 2015 [cited by applicant]
US 20150112602A1 · Kural et al. · 2015 [cited by applicant]
US 20150112658A1 · Kural et al. · 2015 [cited by applicant]
US 20150197815A1 · Kural · 2015 [cited by applicant]
US 20150199472A1 · Kural · 2015 [cited by applicant]
US 20150199473A1 · Kural · 2015 [cited by applicant]
US 20150199474A1 · Kural · 2015 [cited by applicant]
US 20150199475A1 · Kural · 2015 [cited by applicant]
US 20150227685A1 · Kural · 2015 [cited by applicant]
US 20150293994A1 · Kelly · 2015 [cited by applicant]
US 20150302145A1 · Kural et al. · 2015 [cited by applicant]
US 20150310167A1 · Kural et al. · 2015 [cited by applicant]
US 20150344970A1 · Vogelstein et al. · 2015 [cited by applicant]
US 20150347678A1 · Kural · 2015 [cited by applicant]
US 20150356147A1 · Mishra et al. · 2015 [cited by applicant]
US 20160259880A1 · Semenyuk · 2016 [cited by applicant]
US 20160306921A1 · Kural · 2016 [cited by applicant]
US 20160342737A1 · Kaye · 2016 [cited by applicant]
US 20160355881A1 · Wangh et al. · 2016 [cited by applicant]
US 20160364523A1 · Locke et al. · 2016 [cited by applicant]
US 20170058320A1 · Locke et al. · 2017 [cited by applicant]
US 20170058341A1 · Locke et al. · 2017 [cited by applicant]
US 20170058365A1 · Locke et al. · 2017 [cited by applicant]
US 20170198351A1 · Lee et al. · 2017 [cited by applicant]
US 20170199959A1 · Locke · 2017 [cited by applicant]
US 20170199960A1 · Ghose et al. · 2017 [cited by applicant]
US 20170242958A1 · Brown · 2017 [cited by applicant]
US 20200232029A1 · Locke et al. · 2020 [cited by applicant]
US 20200399719A1 · Locke et al. · 2020 [cited by applicant]
US 20200407778A1 · Locke et al. · 2020 [cited by applicant]
US 20230357842A1 · Locke et al. · 2023 [cited by applicant]
US 20230366046A1 · Locke et al. · 2023 [cited by applicant]
KR 101282798B1 · 2013 [cited by applicant]
WO WO2007086935A2 · 2007 [cited by applicant]
WO WO2010010992A1 · 2010 [cited by applicant]
WO WO2012096579A2 · 2012 [cited by applicant]
WO WO2012098515A1 · 2012 [cited by applicant]
WO WO2012142531A2 · 2012 [cited by applicant]
WO WO2013035904A1 · 2013 [cited by applicant]
WO WO2013043909A1 · 2013 [cited by applicant]
WO WO2013106737A1 · 2013 [cited by applicant]
WO WO2013184643A1 · 2013 [cited by applicant]
WO WO2015027050A1 · 2015 [cited by applicant]
WO WO2015048753A1 · 2015 [cited by applicant]
WO WO2015058093A1 · 2015 [cited by applicant]
WO WO2015058095A1 · 2015 [cited by applicant]
WO WO2015058097A1 · 2015 [cited by applicant]
WO WO2015058120A1 · 2015 [cited by applicant]
WO WO2015061099A1 · 2015 [cited by applicant]
WO WO2015061103A1 · 2015 [cited by applicant]
WO WO2015105963A1 · 2015 [cited by applicant]
WO WO2015123269A1 · 2015 [cited by applicant]
WO WO2016141294A1 · 2016 [cited by applicant]
WO WO2016201215A1 · 2016 [cited by applicant]
WO WO2017120128A1 · 2017 [cited by applicant]
WO WO2017123864A1 · 2017 [cited by applicant]
WO WO2017147124A1 · 2017 [cited by applicant]
Li, Yuanyuan, and Trygve O. Tollefsbol. “DNA methylation detection: bisulfite genomic sequencing analysis.” Epigenetics protocols (2011): 11-21. [cited by examiner]
Communication pursuant to Article 94(3) EPC issued Apr. 21, 2017 in European Application No. 14803268.3. [cited by applicant]
Examination Report issued Mar. 1, 2018 for Singapore Application No. 11201601124Y. [cited by applicant]
Extended European Search Report issued Mar. 29, 2017 in European Application No. 14837955.5. [cited by applicant]
Extended European Search Report issued May 9, 2017 in European Application No. 14847490.1. [cited by applicant]
Extended European Search Report issued Apr. 12, 2017 in European Application No. 14854801.9. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2014/052065 mailed Feb. 23, 2016. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2014/061158 mailed Feb. 4, 2015. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2014/058328 mailed Dec. 30, 2014. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2014/061198 mailed Feb. 4, 2015. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2014/061162 mailed Mar. 19, 2015. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/057324 mailed Jan. 10, 2017. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/036873 mailed Sep. 7, 2016. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2014/061156 mailed Feb. 17, 2015. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2014/052065 mailed Dec. 11, 2014. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2014/060680 mailed Jan. 27, 2015. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2014/060690 mailed Feb. 10, 2015. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2015/010604 mailed Mar. 31, 2015. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2015/015375 mailed May 11, 2015. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/020899 mailed May 5, 2016. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2017/013329 mailed Apr. 7, 2017. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2017/012015 mailed Apr. 19, 2017. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2017/018830 mailed Aug. 31, 2017. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2015/054461 mailed Jan. 5, 2016. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2016/033201 mailed Sep. 2, 2016 (14 pages). [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2015/048891 mailed Nov. 17, 2015. [cited by applicant]
Written Opinion issued Dec. 21, 2016 for Singapore Application No. 11201601124Y. [cited by applicant]
Written Opinion issued May 29, 2017 for Singapore Application No. 11201602903X. [cited by applicant]
Written Opinion issued Jun. 12, 2017 for Singapore Application No. 11201603039P. [cited by applicant]
Written Opinion issued Jul. 10, 2017 for Singapore Application No. 11201603044S. [cited by applicant]
Written Opinion issued Jun. 15, 2017 for Singapore Application No. 11201605506Q. [cited by applicant]
[No Author Listed], BCF2 Quick Reference (r198). http://samtools.github.io/hts-specs/BCFv2_gref.pdf [last accessed Nov. 13, 2019]. 1 page. [cited by applicant]
[No Author Listed], Directed acyclic graph. 2013. 6 pages. https://atozwiki.com/Directed_acyclic_graph [Last accessed Jul. 27, 2022]. [cited by applicant]
[No Author Listed], The Variant Call Formal (VCF) Version 4.2 Specification. Jul. 8, 2019. https://samtools.github.io/hts-specs/VCFv4.2.pdf [last accessed Nov. 15, 2019]. 28 pages. [cited by applicant]
Abouelhoda et al., Integrating Taverna and Galaxy workflows with cloud computing support. BMC bioinformatics. Dec. 2012;13(1):77. [cited by applicant]
Agarwal et al., Social interaction network extractor from text. InThe Companion Volume of the Proceedings of IJCNLP 2013: System Demonstrations Oct. 2013: pp. 33-36. [cited by applicant]
Aguiar et al., HapCompass: a fast cycle basis algorithm for accurate haplotype assembly of sequence data. Journal of Computational Biology. Jun. 1, 2012;19(6):577-90. [cited by applicant]
Aguiar et al., Haplotype assembly in polyploid genomes and identical by descent shared tracts. Bioinformatics. Jun. 19, 2013;29(13):1352-60. [cited by applicant]
Airoldi et al., Mixed membership stochastic blockmodels. Journal of machine learning research. 2008;9(Sep.):1981-2014. [cited by applicant]
Albers et al., accurate indel calls from short-read data. Genome research. Jun. 1, 2011;21(6):961-73. [cited by applicant]
Alioto et al., A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing. Nature communications. Dec. 9, 2015;6:10001. [cited by applicant]
Altera, Implementation of the Smith-Waterman algorithm on reconfigurable supercomputing platform, White Paper ver 1.0. 2007 (18 pages). [cited by applicant]
Altschul et al., Optimal sequence alignment using affine gap costs. Bulletin of mathematical biology. Jan. 1, 1986;48(5-6):603-16. [cited by applicant]
Auton et al., the 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature. Oct. 2015;526(7571):68-74. [cited by applicant]
Bansal et al., An MCMC algorithm for haplotype assembly from whole-genome sequence data. Genome research. Aug. 1, 2008;18(8):1336-46. [cited by applicant]
Bao et al., BRANCH: boosting RNA-Seq assemblies with partial or related genomic sequences. Bioinformatics. Mar. 14, 2013;29(10):1250-9. [cited by applicant]
Barbieri et al., Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nature genetics. Jun. 2012;44(6):685-689. [cited by applicant]
Beerenwinkel et al., Conjunctive bayesian networks. Bernoulli. 2007;13(4):893-909. [cited by applicant]
Berlin et al., Assembling large genomes with single-molecule sequencing and locality-sensitive hashing. Nature biotechnology. Jun. 2015;33(6):623.bioRxiv preprint (35 pages); retrieved from the internet on Jan. 29, 2015… [cited by applicant]
Bertone et al., Global identification of human transcribed sequences with genome tiling arrays. Science. Dec. 24, 2004;306(5705):2242-6. [cited by applicant]
Bertrand et al., Genetic map refinement using a comparative genomic approach. Journal of Computational Biology. Oct. 1, 2009;16(10):1475-86. [cited by applicant]
Black, A simple answer for a splicing conundrum. Proceedings of the National Academy of Sciences. Apr. 5, 2005;102(14):4927-8. [cited by applicant]
Borozan et al., Evaluation of alignment algorithms for discovery and identification of pathogens using RNA-Seq. PloS one. Oct. 30, 2013;8(10):e76935. 17 pages. [cited by applicant]
Boyer et al., A fast string searching algorithm. Communications of the ACM. Oct. 1, 1977;20(10):762-72. [cited by applicant]
Browning et al., Haplotype phasing: existing methods and new developments. Nature Reviews Genetics. Oct. 2011;12(10):703. [cited by applicant]
Buhler et al., Search algorithms for biosequences using random projection. University of Washington; Aug. 2001. (203 pages); retreived from the internet on Jun. 3, 2016, at <http://www.mathcs.emory.edu/˜cheung/papers/Ma… [cited by applicant]
Caboche et al., Comparison of mapping algorithms used in high-throughput sequencing: application to Ion Torrent data. BMC genomics. Dec. 2014;15(1):264. [cited by applicant]
Carig et al., Ordering of cosmid clones covering the herpes simplex virus type I (HSV-I) genome: a test case for fingerprinting by hybridisation. Nucleic acids research. May 1, 1990;18(9):2653-60. [cited by applicant]
Carrington et al., Polypeptide ligation occurs during post-translational modification of concanavalin A. Nature. Jan. 1985;313(5997):64. [cited by applicant]
Cartwright, DNA assembly with gaps (Dawg): simulating sequence evolution. Bioinformatics. Nov. 1, 2005;21(Suppl_3):iii31-8. [cited by applicant]
Chang, The application of alternative splicing graphs in quantitative analysis of alternative splicing form from EST database, Int J Comp Appl Tech. 2005; 22(1):14. [cited by applicant]
Chen, Transient hypermutability, chromothripsis and replication-based mechanisms in the generation of concurrent clustered mutations, Mutation Res. 2012; 750(1):562-59. [cited by applicant]
Chin et al., Nonhybrid, finished microbial genome assemblies from long-read SMRT sequencing data. Nature methods. Jun. 2013;10(6):563-569. [cited by applicant]
Chuang et al., Gene recognition based on DAG shortest paths. Bioinformatics. Jun. 1, 2001;17(suppl_1):S56-64. [cited by applicant]
Clark, 2014, Illumina announces landmark $1,000 human genome sequencing, Wired, Jan. 15, 2014. [cited by applicant]
Cock et al., Galaxy tools and workflows for sequence analysis with applications in molecular plant pathology. PeerJ. Sep. 17, 2013;1:e167. [cited by applicant]
Cohen-Boulakia et al., Distilling structure in Taverna scientific workflows: a refactoring approach. BMC bioinformatics. Jan. 2014;15(1):S12. [cited by applicant]
Compeau et al., How to apply de Bruijn graphs to genome assembly. Nature biotechnology. Nov. 2011;29(11):987-991. [cited by applicant]
Cormen et al., Introduction to Algorithms. Third Edition. The MIT Press. 2009. 6 pages. [cited by applicant]
Costa, Uncovering the Complexity of Transcriptomes with RNA-Seq, J Biomed Biotech. 2010; 853916. [cited by applicant]
Craddock et al., Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. May 11, 2007;447:661-78. [cited by applicant]
Crochemore et al., Direct Construction of Compact Directed Acyclic Word Graphs. Springer, Berlin, Heidelberg. 1997:116-29. [cited by applicant]
Croft et al., The Use of Phrases and Structured Queries in Information Retrieval. Proceedings of the 14th Annual International ACM SIGIR Conference on Research and Development in Information Retrieval. 1991:32-45. [cited by applicant]
Danecek et al., The variant call format and VCFtools. Bioinformatics. Jun. 7, 2011;27(15):2156-8. [cited by applicant]
Delcher et al., Alignment of whole genomes. Nucleic acids research. Jan. 1, 1999;27(11):2369-76. [cited by applicant]
Denoeud et al., Identification of polymorphic tandem repeats by direct comparison of genome sequence from different bacterial strains: a web-based resource. BMC bioinformatics. Dec. 2004;5(1):4. [cited by applicant]
DePristo et al., A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nature genetics. May 2011;43(5):491-498. [cited by applicant]
Dinov et al., Applications of the pipeline environment for visual informatics and genomics computations. BMC bioinformatics. Dec. 2011;12(1):304. [cited by applicant]
Do et al., Compressed Directed Acyclic Word Graph with Application in Local Alignment. Algorithmica. 2013;67:125-41. [cited by applicant]
Duan et al., Optimizing de novo common wheat transcriptome assembly using short-read RNA-Seq data. BMC genomics. Dec. 2012;13(1):392. [cited by applicant]
Dudley et al., A quick guide for developing effective bioinformatics programming skills. PLOS computational biology. Dec. 24, 2009;5(12):e1000589. [cited by applicant]
Durbin, Efficient haplotype matching and storage using the positional Burrows-Wheeler transform (PBWT). Bioinformatics. Jan. 9, 2014;30(9):1266-72. [cited by applicant]
Durham et al., EGene: a configurable pipeline generation system for automated sequence analysis. Bioinformatics. Apr. 6, 2005;21(12):2812-3. [cited by applicant]
Endelman JB. New algorithm improves fine structure of the barley consensus SNP map. BMC genomics. Dec. 2011;12(1):407. [cited by applicant]
Farrar, Striped Smith-Waterman speeds database searches six times over other SIMD implementations. Bioinformatics. Nov. 16, 2006;23(2):156-61. [cited by applicant]
Fiers et al., High-throughput bioinformatics with the Cyrille2 pipeline system. BMC bioinformatics. Dec. 2008;9(1):96. [cited by applicant]
Fitch, Distinguishing homologous from analogous proteins. Systematic zoology. Jun. 1, 1970;19(2):99-113. [cited by applicant]
Flicek et al., Sense from sequence reads: methods for alignment and assembly. Nature methods. Oct. 15, 2009;6(11s):S6-S12. [cited by applicant]
Florea et al., Gene and alternative splicing annotation with AIR. Genome research. Jan. 1, 2005;15(1):54-66. [cited by applicant]
Florea et al., Genome-guided transcriptome assembly in the age of next-generation sequencing. IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB). Sep. 1, 2013;10(5):1234-40. [cited by applicant]
Floyd, Algorithm 245: treesort. Communications of the ACM. Dec. 1, 1964;7(12):701. [cited by applicant]
Garber et al., Computational methods for transcriptome annotation and quantification using RNA-seq. Nature methods. Jun. 2011;8(6):469-477. [cited by applicant]
Gerlinger et al., Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. New England journal of medicine. Mar. 8, 2012;366(10):883-92. [cited by applicant]
Glusman et al., Whole-genome haplotyping approaches and genomic medicine. Genome medicine. Dec. 2014;6(9):73. [cited by applicant]
Golub et al., Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. science. Oct. 15, 1999;286(5439):531-7. [cited by applicant]
Goto et al., BioRuby: bioinformatics software for the Ruby programming language. Bioinformatics. Aug. 25, 2010;26(20):2617-9. [cited by applicant]
Gotoh, An improved algorithm for matching biological sequences. Journal of molecular biology. Dec. 15, 1982;162(3):705-8. [cited by applicant]
Gotoh, Multiple sequence alignment: algorithms and applications. Advances in biophysics. Jan. 1, 1999;36:159-206. [cited by applicant]
Grabherr et al., Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nature biotechnology. Jul. 2011;29(7):644-654. [cited by applicant]
Grasso et al., Combining partial order alignment and progressive multiple sequence alignment increases alignment speed and scalability to very large alignment problems. Bioinformatics. Feb. 12, 2004;20(10):1546-56. [cited by applicant]
Guttman et al., Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs. Nature biotechnology. May 2010;28(5):503-510. [cited by applicant]
Guttman, Ab initio reconstruction of transcriptomes of pluripotent and lineage committed cells reveals gene structures of thousands of lincRNAs, NIH-PA Author Manuscript. 2010. [cited by applicant]
Haas et al., DAGchainer: a tool for mining segmental genome duplications and synteny. Bioinformatics. Jul. 9, 2004;20(18):3643-6. [cited by applicant]
HapMap International Consortium. A haplotype map of the human genome. Nature. 2005;437:1299-320. [cited by applicant]
Harenberg et al., Community detection in large-scale networks: a survey and empirical evaluation. Wiley Interdisciplinary Reviews: Computational Statistics. Nov. 2014;6(6):426-39. [cited by applicant]
Harrow et al., GENCODE: the reference human genome annotation for The ENCODE Project. Genome research. Sep. 1, 2012;22(9):1760-74. [cited by applicant]
He et al., Optimal algorithms for haplotype assembly from whole-genome sequence data. Bioinformatics. Jun. 1, 2010;26(12):i183-90. [cited by applicant]
Heber et al., Splicing graphs and EST assembly problem. Bioinformatics. Jul. 1, 2002;18(suppl_1):S181-8. [cited by applicant]
Hein, A new method that simultaneously aligns and reconstructs ancestral sequences for any number of homologous sequences, when the phylogeny is given. Molecular Biology and Evolution. Nov. 1, 1989;6(6):649-68. [cited by applicant]
Hein, A tree reconstruction method that is economical in the number of pairwise comparisons used. Molecular biology and evolution. Nov. 1, 1989;6(6):669-84. [cited by applicant]
Hendren et al., Parallelizing Programs with Recursive Data Structures. IEEE Transactions on Parallel and Distributed Systems. 1990;1(1):35-47. [cited by applicant]
Hokamp et al., Wrapping up BLAST and other applications for use on Unix clusters. Bioinformatics. Feb. 12, 2003;19(3):441-2. [cited by applicant]
Holland et al., BioJava: an open-source framework for bioinformatics. Bioinformatics. Aug. 8, 2008;24(18):2096-7. [cited by applicant]
Homer et al., Improved variant discovery through local re-alignment of short-read next-generation sequencing data using SRMA. Genome biology. Oct. 2010;11(10):R99. [cited by applicant]
Hoon et al., Biopipe: a flexible framework for protocol-based bioinformatics analysis. Genome Research. Aug. 1, 2003;13(8):1904-15. [cited by applicant]
Horspool, Practical fast searching in strings. Software: Practice and Experience. Jun. 1980;10(6):501-6. [cited by applicant]
Huang, 3: Bio-Sequence Comparison and Alignment, ser. Curr Top Comp Mol Biol. Cambridge, Mass.: The MIT Press. 2002:45-69. [cited by applicant]
Huddleston et al., A new data structure for representing sorted lists. Acta informatica. Jun. 1, 1982;17(2):157-84. [cited by applicant]
Hull et al., Taverna: a tool for building and running workflows of services. Nucleic acids research. Jul. 1, 2006;34(suppl_2):W729-32. [cited by applicant]
Hutchinson et al., Allele-specific methylation occurs at genetic variants associated with complex disease. PloS one. Jun. 9, 2014;9(6):e98464. [cited by applicant]
Jones et al., AliWABA: alignment on the web through an A-Bruijn approach. Nucleic Acids Research. 2006;34:613-6. [cited by applicant]
Kano et al., Text mining meets workflow: linking U-Compare with Taverna. Bioinformatics. Aug. 12, 2010;26(19):2486-7. [cited by applicant]
Katoh et al., MAFFT version 5: improvement in accuracy of multiple sequence alignment. Nucleic acids research. Jan. 1, 2005;33(2):511-8. [cited by applicant]
Kawas et al., BioMoby extensions to the Taverna workflow management and enactment software. BMC bioinformatics. Dec. 2006;7(1):523. [cited by applicant]
Kehr et al., Genome alignment with graph data structures: a comparison. BMC bioinformatics. Dec. 2014;15(1):99. [cited by applicant]
Kent, BLAT—the BLAST-like alignment tool. Genome research. Apr. 1, 2002;12(4):656-64. [cited by applicant]
Kim et al., ECgene: genome-based EST clustering and gene modeling for alternative splicing. Genome research. Apr. 1, 2005;15(4):566-76. [cited by applicant]
Kim et al., Introducing EzTaxon-e: a prokaryotic 16S rRNA gene sequence database with phylotypes that represent uncultured species. International Journal of Systematic and Evolutionary Microbiology. 2012;62:716-21. [cited by applicant]
Kim et al., TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome biology. Apr. 2013;14(4):R36. [cited by applicant]
Kim et al.,. A scaffold analysis tool using mate-pair information in genome sequencing. BioMed Research International. Apr. 3, 2008; 8(3): 195-197. [cited by applicant]
Koolen et al., Clinical and molecular delineation of the 17q21. 31 microdeletion syndrome. Journal of medical genetics. Nov. 1, 2008;45(11):710-20. [cited by applicant]
Krabbenhöft et al., Integrating ARC grid middleware with Taverna workflows. Bioinformatics. Mar. 19, 2008;24(9):1221-2. [cited by applicant]
Kuhn et al., CDK-Taverna: an open workflow environment for cheminformatics. Bmc Bioinformatics. Dec. 2010;11(1):159. [cited by applicant]
Kumar et al., Comparing de novo assemblers for 454 transcriptome data. BMC genomics. Dec. 2010;11(1):571. [cited by applicant]
Kurtz et al., Versatile and open software for comparing large genomes. Genome biology. Jan. 2004;5(2):R12. [cited by applicant]
LaFramboise, Single nucleotide polymorphism arrays: a decade of biological, computational and technological advances. Nucleic acids research. Jul. 1, 2009;37(13):4181-93. [cited by applicant]
Lam et al., Compressed indexing and local alignment of DNA. Bioinformatics. Jan. 28, 2008;24(6):791-7. [cited by applicant]
Langmead et al., Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome biology. Mar. 2009;10(3):R25. [cited by applicant]
Lanzén et al., The Taverna Interaction Service: enabling manual interaction in workflows. Bioinformatics. Mar. 12, 2008;24(8):1118-20. [cited by applicant]
Larkin et al., Clustal W and Clustal X version 2.0. bioinformatics. Nov. 1, 2007;23(21):2947-8. [cited by applicant]
Layer et al., Efficient genotype compression and analysis of large genetic-variation datasets. Nature Methods. 2016;13(1):63-5. [cited by applicant]
Lecca et al., Defining order and timing of mutations during cancer progression: the TO-DAG probabilistic graphical model. Frontiers in genetics. Oct. 13, 2015;6:309: 1-17. [cited by applicant]
Lee et al. Accurate read mapping using a graph-based human pan-genome. (May 2015) American Society of Human Genetics 64th Annual Meeting Platform Abstracts; Abstract 41. [cited by applicant]
Lee et al., MOSAIK: a hash-based algorithm for accurate next-generation sequencing short-read mapping. PloS one. Mar. 5, 2014;9(3):e90581. [cited by applicant]
Lee et al., Multiple sequence alignment using partial order graphs. Bioinformatics. Mar. 1, 2002;18(3):452-64. [cited by applicant]
Lee, 2014, Accurate read mapping using a graph-based human pan-genome, ASHG 2014 Abstracts. [cited by applicant]
Lee, Bioinformatics analysis of alternative splicing, Brief Bioinf. 2005;6(1):23-33. [cited by applicant]
Lee, Generating consensus sequences from partial order multiple sequence alignment graphs. Bioinformatics. May 22, 2003;19(8):999-1008. [cited by applicant]
LeGault et al., Inference of alternative splicing from RNA-Seq data with probabilistic splice graphs. Bioinformatics. Jul. 11, 2013;29(18):2300-10. [cited by applicant]
LeGault, 2010, Leaming Probalistic Splice Graphs from RNA-Seq data, pages.cs.wisc.edu/˜legault/cs760_writeup.pdf; retrieved from the internet on Apr. 6, 2014. [cited by applicant]
Leipzig et al., The Alternative Splicing Gallery (ASG): bridging the gap between genome and transcriptome. Nucleic Acids Research. Jan. 1, 2004;32(13):3977-83. [cited by applicant]
Li et al., A survey of sequence alignment algorithms for next-generation sequencing. Briefings in bioinformatics. Sep. 1, 2010;11(5):473-83. [cited by applicant]
Li et al., Automated manipulation of systems biology models using libSBML within Taverna workflows. Bioinformatics. Dec. 1, 2007;24(2):287-9. [cited by applicant]
Li et al., Fast and accurate short read alignment with Burrows-Wheeler transform. bioinformatics. Jul. 15, 2009;25(14):1754-60. [cited by applicant]
Li et al., Performing statistical analyses on quantitative data in Taverna workflows: an example using R and maxdBrowse to identify differentially-expressed genes from microarray data. BMC bioinformatics. Dec. 2008;9(1)… [cited by applicant]
Li et al., SOAP: short oligonucleotide alignment program. Bioinformatics. Jan. 28, 2008;24(5):713-4. [cited by applicant]
Li et al., SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics. Jun. 3, 2009;25(15):1966-7. [cited by applicant]
Li et al., The sequence alignment/map format and SAMtools. Bioinformatics. Aug. 15, 2009;25(16):2078-9. [cited by applicant]
Li et al., TreeFam: a curated database of phylogenetic trees of animal gene families. Nucleic acids research. Jan. 1, 2006;34(suppl_1):D572-80. [cited by applicant]
Li, BGT: efficient and flexible genotype query across many samples. Bioinformatics. arXiv:1506.08452 [q-bio.GN]. Bioinformatics. 2015;32(4):590-2. [cited by applicant]
Li, Towards Better Understanding of Artificats in Variant Calling from High-Coverage Samples. Bioinformatics. arXiv:1404.0929 [q-bio.GN]. 2015. 8 pages. [cited by applicant]
Life Technologies, 2013, Rapid Exome Sequencing Using the Ion Proton System and Ion Ampliseq Technology, Applicalion Note (5 Pages). [cited by applicant]
Lindgreen, AdapterRemoval: easy cleaning of next-generation sequencing reads. BMC research notes. Dec. 2012;5(1):337. [cited by applicant]
Lipman et al., Rapid and sensitive protein similarity searches. Science. Mar. 22, 1985;227(4693):1435-41. [cited by applicant]
Lücking et al., PICS-Ord: unlimited coding of ambiguous regions by pairwise identity and cost scores ordination. BMC bioinformatics. Dec. 2011;12(1):10. [cited by applicant]
Lupski et al., Genomic disorders: molecular mechanisms for rearrangements and conveyed phenotypes. PLoS genetics. Dec. 30, 2005;1(6):e49. [cited by applicant]
Ma et al., Multiple genome alignment based on longest path in directed acyclic graphs. International journal of bioinformatics research and applications. Oct. 1, 2010;6(4):366-83. [cited by applicant]
Machine translation of KR 10-1282798 B1 generated on Jan. 6, 2016, by the website of the European Patent Office (23 pages). [cited by applicant]
Machine translation produced on Jun. 1, 2015, by Espacenet of WO 2010/010992 A1 (11 pages). [cited by applicant]
Machine translation produced on Jun. 1, 2015, by WPIO website of WO 2013/035904 (10 pages). [cited by applicant]
Mamoulis, 2004, Non-contiguous sequence pattern queries, in Advances in Database Technology—EDBT 2004: 9th Intemational Conference on Extending Database Technology, Heraklion, Crete, Greece, Mar. 14-18, 2004, Proceeding… [cited by applicant]
Manolio, Genomewide association studies and assessment of the risk of disease. New England journal of medicine. Jul. 8, 2010;363(2):166-76. [cited by applicant]
Mardis, The $1,000 genome, the $100,000 analysis?, Genome Med. 2010;2:84-85. [cited by applicant]
Margulies et al., Genome sequencing in microfabricated high-density picolitre reactors. Nature. Sep. 2005;437(7057):376-380. [cited by applicant]
Marth et al., A general approach to single-nucleotide polymorphism discovery. Nature genetics. Dec. 1999;23(4):452. [cited by applicant]
Mazrouee et al., FastHap: fast and accurate single individual haplotype reconstruction using fuzzy conflict graphs. Bioinformatics. Aug. 22, 2014;30(17):i371-8. [cited by applicant]
McKenna et al., The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome research. Sep. 1, 2010;20(9):1297-303. [cited by applicant]
McSherry, Spectral partitioning of random graphs. InProceedings 42nd IEEE Symposium on Foundations of Computer Science Oct. 8, 2001 (pp. 529-537). IEEE. [cited by applicant]
Miller et al., Assembly algorithms for next-generation sequencing data. Genomics. Jun. 1, 2010;95(6):315-27. [cited by applicant]
Misra et al., Anatomy of a hash-based long read sequence mapping algorithm for next generation DNA sequencing. Bioinformatics. Nov. 18, 2010;27(2):189-95. [cited by applicant]
Missier, 2010, Taverna, reloaded, Proc. Scientific and Statistical Database Management, 22nd Int Conf, Heidelberg, Germany, Jun./ Jul. 2010, Gertz & Ludascher, Eds., Springer. [cited by applicant]
Moudrianakis et al., Base sequence determination in nucleic acids with the electron microscope, III. Chemistry and microscopy of guanine-labeled DNA. Proceedings of the National Academy of Sciences of the United States … [cited by applicant]
Mount, Multiple Sequence Alignment, Bioinformatics, 2001, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. 2001; pp. 139-204. [cited by applicant]
Mourad et al., A hierarchical Bayesian network approach for linkage disequilibrium modeling and data-dimensionality reduction prior to genome-wide association studies. BMC bioinformatics. Dec. 2011;12(1):16: 1-20. [cited by applicant]
Myers, The fragment assembly string graph. Bioinformatics. Jan. 1, 2005;21(suppl_2):ii79-85. [cited by applicant]
Nagalakshmi et al., RNA-Seq: a method for comprehensive transcriptome analysis. Current protocols in molecular biology. Jan. 2010;89(1):4-11. [cited by applicant]
Nagarajan, Sequence assembly demystified, Nat Rev. 2013;14:157-167. [cited by applicant]
Najafi et al., Fundamental Limits of Pooled-DNA Sequencing. arXiv preprint arXiv:1604.04735. Apr. 16, 2016. [cited by applicant]
Nakao et al., Large-scale analysis of human alternative protein isoforms: pattern classification and correlation with subcellular localization signals. Nucleic acids research. Jan. 1, 2005;33(8):2355-63. [cited by applicant]
Needleman et al., A general method applicable to the search for similarities in the amino acid sequence of two proteins. Journal of molecular biology. Mar. 28, 1970;48(3):443-53. [cited by applicant]
Nenadic, 2010, Nested Workflows, The Taverna Knowledge Blog, Dec. 13, 2010. Retrieved on Feb. 25, 2016 from http://taverna.knowledgeblog.org/2010/12/13/nested-workflows/. [cited by applicant]
Neumann, Efficient Generation and Execution of DAG-Structured Query Graphs. Doctoral Dissertation. Universitat Mannheim. 2005. 170 pages. [cited by applicant]
Newman et al., An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nature medicine. May 2014;20(5):548: 1-11. [cited by applicant]
Newman, Community detection and graph partitioning. arXiv:1305.4974v1. EPL (Europhysics Letters). Aug. 9, 2013;103(2):28003. [cited by applicant]
Ning et al., SSAHA: a fast search method for large DNA databases. Genome research. Oct. 1, 2001;11(10):1725-9. [cited by applicant]
Oinn et al., Taverna: a tool for the composition and enactment of bioinformatics workflows. Bioinformatics. Jun. 17, 2004;20(17):3045-54. [cited by applicant]
Oinn et al., Taverna: lessons in creating a workflow environment for the life sciences. Concurrency and Computation: Practice and Experience. Aug. 25, 2006;18(10):1067-100. [cited by applicant]
Olsson et al., Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. EMBO molecular medicine. Aug. 1, 2015;7(8):1034-47. [cited by applicant]
O'Rawe et al., Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing. Genome medicine. Dec. 2013;5(3):28. [cited by applicant]
Oshlack et al., From RNA-seq reads to differential expression results. Genome biology. Dec. 2010;11(12):220. [cited by applicant]
Pabinger, A survey of tools for variant analysis of next-generation genome sequencing data, Brief Bioinf. 2013. [cited by applicant]
Parks et al., Detecting non-allelic homologous recombination from high-throughput sequencing data. Genome biology. Dec. 2015;16(1):72. [cited by applicant]
Paten et al., Cactus graphs for genome comparisons. Journal of Computational Biology. Mar. 1, 2011;18(3):469-81. [cited by applicant]
Paterson et al., An XML transfer schema for exchange of genomic and genetic mapping data: implementation as a web service in a Taverna workflow. BMC bioinformatics. Dec. 2009;10(1):252. [cited by applicant]