title: Coalescent inference for infectious disease: meta-analysis of hepatitis C.
abstract: Genetic analysis of pathogen genomes is a powerful approach to investigating the population dynamics and epidemic history of infectious diseases. However, the theoretical underpinnings of the most widely used, coalescent methods have been questioned, casting doubt on their interpretation. The aim of this study is to develop robust population genetic inference for compartmental models in epidemiology. Using a general approach based on the theory of metapopulations, we derive coalescent models under susceptible-infectious (SI), susceptible-infectious-susceptible (SIS) and susceptible-infectious-recovered (SIR) dynamics. We show that exponential and logistic growth models are equivalent to SI and SIS models, respectively, when co-infection is negligible. Implementing SI, SIS and SIR models in BEAST, we conduct a meta-analysis of hepatitis C epidemics, and show that we can directly estimate the basic reproductive number (R(0)) and prevalence under SIR dynamics. We find that differences in genetic diversity between epidemics can be explained by differences in underlying epidemiology (age of the epidemic and local population density) and viral subtype. Model comparison reveals SIR dynamics in three globally restricted epidemics, but most are better fit by the simpler SI dynamics. In summary, metapopulation models provide a general and practical framework for integrating epidemiology and population genetics for the purposes of joint inference.
authors: Nuffield Department of Clinical Medicine, Experimental Medicine Division, University of Oxford, Oxford, UK.
authors: Bethany
authors: B
authors: Dearlove
authors: Daniel J
authors: DJ
authors: Wilson
mesh_terms: D019143:Evolution, Molecular; D014644:Genetic Variation; D005828:Genetics, Population; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000453:epidemiology* / Q000821:virology*; D006801:Humans; D008962:Models, Theoretical; D011157:Population Dynamics; D015995:Prevalence
references: Genetics. 2006 Mar;172(3):1411-25
references: 16387887
references: Infect Genet Evol. 2011 Mar;11(2):496-503
references: 21251997
references: J R Soc Interface. 2012 May 7;9(70):997-1007
references: 21920961
references: BMC Evol Biol. 2011 May 19;11:131
references: 21595904
references: J Infect Dis. 2004 Sep 15;190(6):1098-108
references: 15319860
references: Nature. 2009 Jun 25;459(7250):1122-5
references: 19516283
references: Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19359-64
references: 22084096
references: Philos Trans R Soc Lond B Biol Sci. 2010 Jun 27;365(1548):1879-90
references: 20478883
references: J Math Biol. 2008 Mar;56(3):293-310
references: 17668212
references: Theor Popul Biol. 1977 Dec;12(3):253-62
references: 601717
references: Science. 2003 Jun 20;300(5627):1966-70
references: 12766207
references: J Gen Virol. 2004 Nov;85(Pt 11):3173-3188
references: 15483230
references: PLoS Pathog. 2012 Sep;8(9):e1002874
references: 22969423
references: Genetics. 2001 Oct;159(2):893-905
references: 11606561
references: J Mol Evol. 1985;22(2):160-74
references: 3934395
references: Wkly Epidemiol Rec. 1999 Dec 10;74(49):425-7
references: 10645164
references: Science. 2001 May 11;292(5519):1155-60
references: 11303090
references: Genetics. 1999 Dec;153(4):1863-71
references: 10581291
references: Mol Ecol. 2004 Apr;13(4):865-75
references: 15012761
references: Asian Pac J Allergy Immunol. 2009 Jun-Sep;27(2-3):153-60
references: 19839502
references: Nat Genet. 2011 Nov 13;43(12):1275-80
references: 22081229
references: J Med Virol. 2010 Feb;82(2):257-62
references: 20029811
references: N Engl J Med. 2011 Jan 6;364(1):33-42
references: 21142692
references: J Hepatol. 2008 Jan;48(1):148-62
references: 18022726
references: J Viral Hepat. 2008 Jun;15(6):399-408
references: 18248334
references: Science. 2001 Jun 22;292(5525):2323-5
references: 11423661
references: Clin Microbiol Infect. 2011 Feb;17(2):107-15
references: 21091831
references: PLoS Comput Biol. 2012;8(3):e1002413
references: 22412361
references: PLoS One. 2011;6(9):e24889
references: 21931867
references: Science. 2009 Jun 19;324(5934):1557-61
references: 19433588
references: PLoS Comput Biol. 2011 Aug;7(8):e1002136
references: 21901082
references: Theor Popul Biol. 2001 Mar;59(2):133-44
references: 11302758
references: Mol Biol Evol. 2012 Aug;29(8):1969-73
references: 22367748
references: Gastroenterology. 2006 Mar;130(3):703-14
references: 16530512
references: Trends Ecol Evol. 2005 Jan;20(1):39-45
references: 16701339
references: Science. 2004 Jan 16;303(5656):327-32
references: 14726583
references: Mol Biol Evol. 2003 Mar;20(3):381-7
references: 12644558
references: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15584-9
references: 12438687
references: Syst Biol. 2010 Jan;59(1):27-41
references: 20525618
references: J Theor Biol. 1994 Sep 7;170(1):95-114
references: 7967636
references: PLoS One. 2009;4(3):e4876
references: 19287490
references: Genetics. 2000 Oct;156(2):879-91
references: 11014833
references: J Virol. 2006 May;80(9):4220-6
references: 16611881
references: PLoS Pathog. 2008 Apr 18;4(4):e1000050
references: 18421380
references: Nature. 2006 Jul 27;442(7101):448-52
references: 16642006
references: Theor Popul Biol. 2004 Nov;66(3):219-32
references: 15465123
references: Genetics. 2009 Dec;183(4):1421-30
references: 19797047
references: J Viral Hepat. 2011 Jan;18(1):42-52
references: 20196805
references: J Gen Virol. 1997 Feb;78 ( Pt 2):321-8
references: 9018053
references: J Gen Virol. 2006 Jan;87(Pt 1):73-82
references: 16361419
references: Genetics. 2000 Jul;155(3):1429-37
references: 10880500
references: Mol Biol Evol. 2012 Jan;29(1):347-57
references: 21890480
references: Lancet Infect Dis. 2005 Sep;5(9):558-67
references: 16122679
references: Mol Biol Evol. 2005 May;22(5):1185-92
references: 15703244
references: Infect Genet Evol. 2008 Sep;8(5):676-81
references: 18599380
references: Infect Genet Evol. 2005 Mar;5(2):131-9
references: 15639745
references: Evolution. 1999 Jun;53(3):664-676
references: 28565620
references: Theor Popul Biol. 1998 Apr;53(2):166-74
references: 9615475
references: PLoS Med. 2009 Dec;6(12):e1000198
references: 20041120
references: PLoS One. 2011;6(5):e19471
references: 21611129
references: Nat Rev Genet. 2009 Aug;10(8):540-50
references: 19564871
references: J Virol. 2009 Jan;83(2):1071-82
references: 18971279
references: J Viral Hepat. 2007 Sep;14(9):667-74
references: 17697020
references: Genetics. 1991 Oct;129(2):555-62
references: 1743491