Difference between revisions of "Rhinovirus: Dose Response Models"

From QMRAwiki
Jump to: navigation, search
m (Protected "Rhinovirus: Dose Response Models" ([edit=sysop] (indefinite) [move=sysop] (indefinite)))
 
(29 intermediate revisions by 3 users not shown)
Line 2: Line 2:
  
 
<center><big>'''Author: Yin Huang'''</big></center>
 
<center><big>'''Author: Yin Huang'''</big></center>
<center>'''If you want to download this chapter in pdf format, please click [http://wiki.camra.msu.edu/images/7/70/Rhinovirus.pdf here]''' </center>
 
<center>'''If you want to download the excel spreadsheet of tables, please click the captions of tables.  If you want to download a specific figure, just click on the figure'''</center>
 
  
  
 
==='''General overview '''===
 
==='''General overview '''===
  
Rhinoviruses belong to the Picornaviridae family, small icosahedral viruses made of a protein capsid that encases a single-stranded, positive-sense RNA molecule. About 100 different serotypes have been identified and characterized by their own specific antigens.
+
Rhinovirus, a small icosahedral viruses made of a protein capsid that encases a single-stranded, positive-sense RNA molecule, belongs to the Picornaviridae family. About 100 different serotypes have been identified and characterized by their own specific antigens.
  
 
Rhinoviruses are responsible for 30 to 50% of adult colds and 10 to 25% of colds in children. Other cold-causing viruses are adenoviruses, coronaviruses, coxsackieviruses, echoviruses, orthomyxoviruses, paramyxoviruses, respiratory syncytial virus, and enteroviruses, each of which produces infections with slightly different patterns of symptoms and severity. Several of the above-mentioned viruses also account for other more severe illnesses (Bella and Rossmann 1999).
 
Rhinoviruses are responsible for 30 to 50% of adult colds and 10 to 25% of colds in children. Other cold-causing viruses are adenoviruses, coronaviruses, coxsackieviruses, echoviruses, orthomyxoviruses, paramyxoviruses, respiratory syncytial virus, and enteroviruses, each of which produces infections with slightly different patterns of symptoms and severity. Several of the above-mentioned viruses also account for other more severe illnesses (Bella and Rossmann 1999).
Line 18: Line 16:
 
==='''Summary Data'''===
 
==='''Summary Data'''===
  
Hendley et al. (1972) inoculated young adult volunteers over the age of 21 with Rhinovirus type 39 (RV 39), strain SF 299, and rhinovirus type 14 (RV 14), strain SF 765, via intranasal exposure route. Shedding of the challenge virus and/or a fourfold or greater in- crease in titer of serum antibody to a homotypic rhinovirus were accepted as evidence of infection.
+
Hendley et al. (1972) inoculated young adult human volunteers over the age of 21 with Rhinovirus type 39 (RV 39), strain SF 299, and rhinovirus type 14 (RV 14), strain SF 765, via intranasal exposure route. Shedding of the challenge virus and/or a fourfold or greater increase in titer of serum antibody to a homotypic rhinovirus were accepted as evidence of infection.
  
{|
 
| STYLE="vertical-align: top; text-align: center"|
 
{| border = "1"
 
|+ '''Table 6.1. Summary of the rhinovirus data and best fits'''
 
| Experiment number || Reference || Host type/pathogen strain || Route/number of doses || Dose units || Response || Best-fit model || Best-fit parameters || ID<sub>50</sub>
 
|- style="background-color:#cccccc;border-top:none;border-bottom:none;border-left:none;border-right:none;padding:0.0201in;"
 
| 1*
 
| Hendley et al., 1972
 
| humans/ rhinovirus type 14, strain SF 765
 
| oral/6
 
| pfu
 
| infection
 
| Beta-Poisson
 
| α = 0.20
 
N<sub>50</sub> = 9.22
 
| 9.22
 
|-
 
| 2
 
| Hendley et al., 1972
 
| humans/ rhinovirus type 39, strain SF 299
 
| oral/6
 
| pfu
 
| infection
 
| -
 
| α = 0.22
 
N<sub>50</sub> = 1.81
 
| 1.81
 
|}
 
|}
 
  
'''No acceptable fit for experiment 2.'''
+
{{DRSummaryTableStart|agent=Rhinovirus}}
 +
{{DRSummaryTablePreferredModel|expID= 65 |refer=Hendley et al., 1972|reference=Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) [http://www.jstor.org/stable/30108503 Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers]. ''Journal of Infectious Diseases'' '''125''', 243-248.|host= human |agentStrain= type 39
 +
|route= intranasal |nDoses= 6 |doseUnits= TCID50 doses |response=
 +
infection |bestFitModel=beta-Poisson|parameters=&alpha; =  2.21E-01 , N<sub>50</sub> =  1.81E+00 |N50= 1.81E+00 }}
 +
{{DRSummaryTableNonpreferredModel|expID= 64 |refer=Hendley et al., 1972|reference=COMPLETE REF HERE|host= human |agentStrain= type 14
 +
|route= intranasal |nDoses= 6 |doseUnits= TCID50 doses |response=
 +
infection |bestFitModel=beta-Poisson|parameters=&alpha; =  2.01E-01 , N<sub>50</sub> =  9.22E+00 |N50= 9.22E+00 }}
 +
{{DRSummaryTableNonpreferredModel|expID= 310 |refer=Hendley et al., 1972|reference=COMPLETE REF HERE|host= human |agentStrain= type 14
 +
|route= intranasal |nDoses= 6 |doseUnits= TCID50 doses |response=
 +
infection |bestFitModel=beta-Poisson|parameters=&alpha; =  2.52E-01 , N<sub>50</sub> =  3.83E+00 |N50= 3.83E+00 }}
 +
{{DRSummaryTableNonpreferredModel|expID= 311 |refer=Hendley et al., 1972|reference=COMPLETE REF HERE|host= human |agentStrain= type 39
 +
|route= intranasal |nDoses= 6 |doseUnits= TCID50 doses |response=
 +
infection |bestFitModel=beta-Poisson|parameters=&alpha; =  7.01E-01 , N<sub>50</sub> =  1.9E-01 |N50= 1.9E-01 }}
 +
{{DRSummaryTableNonpreferredModel|expID= 312 |refer=Hendley et al., 1972|reference=COMPLETE REF HERE|host= human |agentStrain= type 14
 +
|route= intranasal |nDoses= 6 |doseUnits= TCID50 doses |response=
 +
infection |bestFitModel=beta-Poisson|parameters=&alpha; =  1.81E-01 , N<sub>50</sub> =  2.22E+01 |N50= 2.22E+01 }}
 +
{{DRSummaryTableNonpreferredModel|expID= 313 |refer=Hendley et al., 1972|reference=COMPLETE REF HERE|host= human |agentStrain= type 39
 +
|route= intranasal |nDoses= 6 |doseUnits= TCID50 doses |response=
 +
infection |bestFitModel=beta-Poisson|parameters=&alpha; =  2E-01 , N<sub>50</sub> =  1.05E+01 |N50= 1.05E+01 }}
 +
{{DRSummaryTableNonpreferredModel|expID= 312, 313 |refer=Hendley et al., 1972|reference=COMPLETE REF HERE|host= human |agentStrain= type 14
 +
|route= intranasal |nDoses= 12 |doseUnits= TCID50 doses |response=
 +
infection |bestFitModel=beta-Poisson|parameters=&alpha; =  1.82E-01 , N<sub>50</sub> =  1.38E+01 |N50= 1.38E+01 }}
 +
{{DRSummaryTableEnd}}
 +
 
 +
[[File:Exponential and betapoisson model.jpg|thumb|none|550px]]
 +
 
 +
----
 +
 
 +
==='''Optimization Output for experiment 65'''===
 +
 
 +
{{DRExperimentDataTable5|title=human/type 39 strain SF 299 model data|refer=Hendley et al., 1972|reference=Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) [http://www.jstor.org/stable/30108503 Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers]. ''Journal of Infectious Diseases'' '''125''', 243-248.|pos=Infected|neg=Non-infected |d1=0.05|p1=0|n1=11|t1=11|d2=0.15|p2=2|n2=7|t2=9|d3=0.5|p3=8|n3=16|t3=24|d4=5|p4=5|n4=11|t4=16|d5=50|p5=47|n5=15|t5=62}}
 +
 
 +
 
 +
{{DRFit|title=Goodness of fit and model selection|devE=50.3|devB=6.01|delta=44.3|DFE=4|DFB=3|X2bPbetter=3.84|pbPbetter=2.76e-11|X2GOFe=9.49|pGOFe=3.06e-10|X2GOFb=7.81|pGOFb=0.111|interpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}
 +
 
 +
 
 +
{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations|MLEa=2.24E-01|p5a=9.88E-04|p25a=1.40E-01|p50a=1.53E-01|p950a=3.71E-01|p975a=4.27E-01|p995a=7.63E-01|MLEN=3.29E+00|p5N=1.90E-02|p25N=1.34E+00|p50N=1.59E+00|p950N=7.67E+00|p975N=9.27E+00|p995N=1.59E+01}}
 +
 
 +
 
 +
[[File:BPscatter ID65.png|thumb|left|500px|'''Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:BPmodel ID65.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>
  
 
----
 
----
  
==='''Optimized Models and Fitting Analyses'''===
 
  
'''Optimization Output for experiment 1'''
+
==='''Optimization Output for experiment 64'''===
 +
 
 +
{{DRExperimentDataTable6|title=human/type 14 strain SF 765model data|refer=Hendley et al., 1972|reference=Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) [http://www.jstor.org/stable/30108503 Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers]. ''Journal of Infectious Diseases'' '''125''', 243-248.|pos=Infected|neg=Non-infected|d1=0.5|p1=1|n1=8|t1=9|d2=1.5|p2=4|n2=6|t2=10|d3=5|p3=4|n3=6|t3=10|d4=15|p4=6|n4=4|t4=10|d5=150|p5=27|n5=13|t5=40|d6=300|p6=10|n6=2|t6=12}}
  
{|
 
| STYLE="vertical-align: top; text-align: center"|
 
{| border = "1"
 
|+ [http://wiki.camra.msu.edu/index.php?title=File:Hendley1972_Rhinovirus_datafitconf_1.xls '''Table 6.2:  human/type 14 strain SF 765model data''']
 
| Dose || Infected || Non-infected || Total
 
|-
 
| 3.00E+02 || 10 || 2 || 12
 
|-
 
| 1.50E+02 || 27 || 13 || 40
 
|-
 
| 1.50E+01 || 6 || 4 || 10
 
|-
 
| 5.00E+00 || 4 || 6 || 10
 
|-
 
| 1.50E+00 || 4 || 6 || 10
 
|-
 
| 5.00E-01 || 1 || 8 || 9
 
|-
 
| colspan = "4" | Hendley et al., 1972.
 
|}
 
|}
 
  
 +
{{DRFit|title=Goodness of fit and model selection|devE=51.8|devB=1.68|delta=50.2|DFE=5|DFB=4|X2bPbetter=3.84|pbPbetter=1.42e-12|X2GOFe=11.1|pGOFe=5.8e-10|X2GOFb=9.49|pGOFb=0.794|interpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}
  
{|
 
| STYLE="vertical-align: top; text-align: center"|
 
{| border = "1"
 
|+ [http://wiki.camra.msu.edu/index.php?title=File:Hendley1972_Rhinovirus_datafitconf_1.xls '''Table 6.3: Goodness of fit and model selection''']
 
| Model||Deviance||&Delta;||Degrees <br /> of Freedom||&chi;<sup>2</sup><sub>0.95,1</sub> <br /> ''p-value''||&chi;<sup>2</sup><sub>0.95,m-k</sub> <br /> ''p-value''
 
|-
 
| Exponential
 
| 51.84
 
| rowspan = "2" | 50.16
 
| 5
 
| rowspan = "2" | 3.84 <br /> ''0''
 
| 11.07 <br /> ''0''
 
|-
 
| Beta Poisson
 
| 1.68
 
| 4
 
| 9.49 <br /> ''0.794''
 
|-
 
| colspan = "6" | '''Beta Poisson is best fitting model'''
 
|}
 
| STYLE="vertical-align: top; text-align: center"|
 
{| border = "1"
 
|+ [http://wiki.camra.msu.edu/index.php?title=File:Hendley1972_Rhinovirus_datafitconf_1.xls '''Table 6.4  Optimized parameters for the best fitting (beta Poisson), obtained from 10,000 bootstrap iterations ''']
 
| rowspan = "2" | Parameter
 
| rowspan = "2" | MLE Estimate
 
| colspan = "6" | Percentiles
 
|-
 
| 0.50%||2.5%||5%||95%||97.5%||99.5%
 
|-
 
| &alpha;
 
| 0.20
 
| --
 
| --
 
| --
 
| --
 
| --
 
| --
 
|-
 
| N<sub>50</sub>
 
| 9.22
 
| --
 
| --
 
| --
 
| --
 
| --
 
| --
 
|-
 
| LD<sub>50</sub>
 
| 9.22
 
| 1.42
 
| 2.62
 
| 3.35
 
| 25.38
 
| 31.90
 
| 50.18
 
|}
 
|}
 
  
 +
{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations|MLEa=2.01E-01|p5a=7.76E-02|p25a=1.07E-01|p50a=1.22E-01|p950a=3.36E-01|p975a=3.69E-01|p995a=4.61E-01|MLEN=9.22E+00|p5N=1.41E+00|p25N=2.57E+00|p50N=3.40E+00|p950N=2.47E+01|p975N=3.14E+01|p995N=5.26E+01}}
  
[[File:Hendley1972(1)_Rhinovirus_BPScatter.png|thumb|left|500px|'''Figure 6.1  Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:Hendley1972(1)_Rhinovirus_BPModel.png|thumb|none|500px|'''Figure 6.2  beta Poisson model plot, with confidence bounds around optimized model''']]<br>
+
 
 +
[[File:BPscatter ID64.png|thumb|left|500px|'''Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:BPmodel ID64.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>
  
  
 
----
 
----
  
 +
==='''Optimization Output for experiment 310'''===
 +
 +
{{DRExperimentDataTable6|title=TITLE|refer=Hendley et al., 1972|reference=Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) [http://www.jstor.org/stable/30108503 Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers]. ''Journal of Infectious Diseases'' '''125''', 243-248.|pos=INFECTION|neg=NOT
 +
INFECTION|d1=0.5|p1=1|n1=4|t1=5|d2=1.5|p2=2|n2=3|t2=5|d3=5|p3=3|n3=2|t3=5|d4=15|p4=2|n4=1|t4=3|d5=150|p5=14|n5=5|t5=19|d6=300|p6=5|n6=0|t6=5}}
 +
 +
{{DRFit|title=Goodness of fit and model
 +
selection|devE=29.7|devB=2.42|delta=27.3|DFE=5|DFB=4|X2bPbetter=3.84|pbP
 +
selection|better=1.78e-07|X2GOFe=11.1|pGOFe=1.71e-05|X2GOFb=9.49|pGOFb=0
 +
selection|.658|interpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}
  
'''Optimization Output for experiment 2'''
+
{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 10000 bootstrap
 +
iterations|MLEa=2.52E-01|p5a=9.79E-04|p25a=9.14E-02|p50a=1.16E-01|p950a=5.50E-01|p975a=6.41E-01|p995a=1.06E+00|MLEN=3.83E+00|p5N=9.08E-03|p25N=3.23E-01|p50N=6.41E-01|p950N=1.48E+01|p975N=2.04E+01|p995N=8.86E+01}}
  
{|
+
[[File:BPscatter ID310.png|thumb|left|500px|'''Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:BPmodel ID310.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>
| STYLE="vertical-align: top; text-align: center"|
 
{| border = "1"
 
|+ [http://wiki.camra.msu.edu/index.php?title=File:Hendley1972_Rhinovirus_datafitconf_2.xls '''Table 6.5:  human/type 39 strain SF 299 model data''']
 
| Dose|| Infected || Non-infected || Total
 
|-
 
| 5.00E+01 || 47 || 15 || 62
 
|-
 
| 5.00E+00 || 5 || 11 || 16
 
|-
 
| 1.50E+00 || 22 || 11 || 33
 
|-
 
| 5.00E-01 || 8 || 16 || 24
 
|-
 
| 1.50E-01 || 2 || 7 || 9
 
|-
 
| 5.00E-02 || 0  || 11 || 11
 
|-
 
| colspan = "4" | Hendley et al., 1972.
 
|}
 
|}
 
  
  
{|
+
----
| STYLE="vertical-align: top; text-align: center"|
 
{| border = "1"
 
|+ [http://wiki.camra.msu.edu/index.php?title=File:Hendley1972_Rhinovirus_datafitconf_2.xls '''Table 6.6: Goodness of fit and model selection''']
 
| Model||Deviance||&Delta;||Degrees <br /> of Freedom||&chi;<sup>2</sup><sub>0.95,1</sub> <br /> ''p-value''||&chi;<sup>2</sup><sub>0.95,m-k</sub> <br /> ''p-value''
 
|-
 
| Exponential
 
| 129.77
 
| rowspan = "2" | 117.41
 
| 5
 
| rowspan = "2" | 3.84 <br /> ''0''
 
| 11.07 <br /> ''0''
 
|-
 
| Beta Poisson
 
| 12.36
 
| 4
 
| 9.49 <br /> ''0.149''
 
|-
 
| colspan = "6" | '''Beta Poisson is best fitting model'''
 
|}
 
| STYLE="vertical-align: top; text-align: center"|
 
{| border = "1"
 
|+ [http://wiki.camra.msu.edu/index.php?title=File:Hendley1972_Rhinovirus_datafitconf_1.xls '''Table 6.7  Optimized parameters for the best fitting (beta Poisson), obtained from 10,000 bootstrap iterations ''']
 
| rowspan = "2" | Parameter
 
| rowspan = "2" | MLE Estimate
 
| colspan = "6" | Percentiles
 
|-
 
| 0.50%||2.5%||5%||95%||97.5%||99.5%
 
|-
 
| &alpha;
 
| 0.22
 
| --
 
| --
 
| --
 
| --
 
| --
 
| --
 
|-
 
| N<sub>50</sub>
 
| 1.81
 
| --
 
| --
 
| --
 
| --
 
| --
 
| --
 
|-
 
| LD<sub>50</sub>
 
| 1.81
 
| 0.69
 
| 0.87
 
| 0.98
 
| 3.76
 
| 4.52
 
| Inf
 
|}
 
|}
 
  
 +
==='''Optimization Output for experiment 311'''===
  
[[File:Hendley1972(2)_Rhinovirus_BPScatter.png|thumb|left|500px|'''Figure 6.3  Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:Hendley1972(2)_Rhinovirus_BPModel.png|thumb|none|500px|'''Figure 6.4  beta Poisson model plot, with confidence bounds around optimized model''']]<br>
+
{{DRExperimentDataTable6|title=TITLE|refer=Hendley et al., 1972|reference=Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) [http://www.jstor.org/stable/30108503 Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers]. ''Journal of Infectious Diseases'' '''125''', 243-248.|pos=INFECTION|neg=NOT
 +
INFECTION|d1=0.05|p1=0|n1=2|t1=2|d2=0.15|p2=1|n2=3|t2=4|d3=0.5|p3=5|n3=2|t3=7|d4=1.5|p4=18|n4=1|t4=19|d5=5|p5=1|n5=0|t5=1|d6=50|p6=19|n6=1|t6=20}}
  
 +
{{DRFit|title=Goodness of fit and model
 +
selection|devE=61.7|devB=4.95|delta=56.8|DFE=5|DFB=4|X2bPbetter=3.84|pbP
 +
selection|better=4.85e-14|X2GOFe=11.1|pGOFe=5.32e-12|X2GOFb=9.49|pGOFb=0
 +
selection|.293|interpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}
 +
 +
{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 10000 bootstrap
 +
iterations|MLEa=7.01E-01|p5a=2.29E-01|p25a=3.14E-01|p50a=3.63E-01|p950a=1.81E+06|p975a=3.82E+06|p995a=1.41E+07|MLEN=1.9E-01|p5N=2.27E-02|p25N=5.85E-02|p50N=7.93E-02|p950N=4.20E-01|p975N=4.52E-01|p995N=5.56E-01}}
 +
 +
[[File:BPscatter ID311.png|thumb|left|500px|'''Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:BPmodel ID311.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>
  
  
 
----
 
----
 +
 +
==='''Optimization Output for experiment 312'''===
 +
 +
{{DRExperimentDataTable6|title=TITLE|refer=Hendley et al., 1972|reference=Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) [http://www.jstor.org/stable/30108503 Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers]. ''Journal of Infectious Diseases'' '''125''', 243-248.|pos=INFECTION|neg=NOT
 +
INFECTION|d1=0.5|p1=0|n1=4|t1=4|d2=1.5|p2=2|n2=3|t2=5|d3=5|p3=1|n3=4|t3=5|d4=15|p4=4|n4=3|t4=7|d5=150|p5=13|n5=8|t5=21|d6=300|p6=5|n6=2|t6=7}}
 +
 +
{{DRFit|title=Goodness of fit and model
 +
selection|devE=24.3|devB=2.77|delta=21.5|DFE=5|DFB=4|X2bPbetter=3.84|pbP
 +
selection|better=3.56e-06|X2GOFe=11.1|pGOFe=0.000194|X2GOFb=9.49|pGOFb=0
 +
selection|.597|interpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}
 +
 +
{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 10000 bootstrap
 +
iterations|MLEa=1.81E-01|p5a=3.92E-02|p25a=7.30E-02|p50a=9.02E-02|p950a=4.00E-01|p975a=4.79E-01|p995a=7.28E-01|MLEN=2.22E+01|p5N=3.12E+00|p25N=5.01E+00|p50N=6.38E+00|p950N=1.22E+02|p975N=2.06E+02|p995N=1.26E+03}}
 +
 +
[[File:BPscatter ID312.png|thumb|left|500px|'''Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:BPmodel ID312.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>
 +
 +
 +
----
 +
 +
==='''Optimization Output for experiment 313'''===
 +
 +
{{DRExperimentDataTable6|title=TITLE|refer=Hendley et al., 1972|reference=Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) [http://www.jstor.org/stable/30108503 Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers]. ''Journal of Infectious Diseases'' '''125''', 243-248.|pos=INFECTION|neg=NOT
 +
INFECTION|d1=0.05|p1=0|n1=4|t1=4|d2=0.15|p2=1|n2=4|t2=5|d3=0.5|p3=3|n3=14|t3=17|d4=1.5|p4=4|n4=10|t4=14|d5=5|p5=4|n5=11|t5=15|d6=50|p6=28|n6=14|t6=42}}
 +
 +
{{DRFit|title=Goodness of fit and model
 +
selection|devE=29.2|devB=2.93|delta=26.2|DFE=5|DFB=4|X2bPbetter=3.84|pbP
 +
selection|better=3.05e-07|X2GOFe=11.1|pGOFe=2.16e-05|X2GOFb=9.49|pGOFb=0
 +
selection|.569|interpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}
 +
 +
{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 10000 bootstrap
 +
iterations|MLEa=2E-01|p5a=7.86E-02|p25a=9.79E-02|p50a=1.11E-01|p950a=4.65E-01|p975a=5.58E-01|p995a=8.66E-01|MLEN=1.05E+01|p5N=3.00E+00|p25N=3.98E+00|p50N=4.65E+00|p950N=3.67E+01|p975N=5.32E+01|p995N=1.22E+02}}
 +
 +
[[File:BPscatter ID313.png|thumb|left|500px|'''Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:BPmodel ID313.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>
 +
 +
 +
----
 +
 +
==='''Optimization Output for pooled experiments of 312&313'''===
 +
 +
{{DRExperimentDataTable12|title=TITLE|refer=Hendley et al., 1972|reference=Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) [http://www.jstor.org/stable/30108503 Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers]. ''Journal of Infectious Diseases'' '''125''', 243-248.|pos=INFECTION|neg=NOT
 +
INFECTION|d1=0.05|p1=0|n1=4|t1=4|d2=0.15|p2=1|n2=4|t2=5|d3=0.5|p3=0|n3=4|t3=4|d4=0.5|p4=3|n4=14|t4=17|d5=1.5|p5=2|n5=3|t5=5|d6=1.5|p6=4|n6=10|t6=14|d7=5|p7=1|n7=4|t7=5|d8=5|p8=4|n8=11|t8=15|d9=15|p9=4|n9=3|t9=7|d10=50|p10=28|n10=14|t10=42|d11=150|p11=13|n11=8|t11=21|d12=300|p12=5|n12=2|t12=7}}"
 +
 +
{{DRFit|title=Goodness of fit and model
 +
selection|devE=78.6|devB=6.22|delta=72.3|DFE=11|DFB=10|X2bPbetter=3.84|p
 +
selection|bPbetter=0|X2GOFe=19.7|pGOFe=2.8e-12|X2GOFb=18.3|pGOFb=0.796|i
 +
selection|nterpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}"
 +
 +
{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 10000 bootstrap
 +
iterations|MLEa=1.82E-01|p5a=1.04E-03|p25a=1.03E-01|p50a=1.14E-01|p950a=3.04E-01|p975a=3.38E-01|p995a=4.09E-01|MLEN=1.38E+01|p5N=2.98E+00|p25N=5.64E+00|p50N=6.67E+00|p950N=3.77E+01|p975N=4.98E+01|p995N=1.32E+02}}
 +
 +
[[File:BPscatter ID312 313.png|thumb|left|500px|'''Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:BPmodel ID312 313.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>
 +
 +
  
 
==='''Summary'''===
 
==='''Summary'''===
  
The responses caused by doses less than one observed in these two experiments should be due to the uncertainties of dose counting in the original study.
+
The responses caused by doses less than one observed in these two experiments are probably due to the uncertainties of dose counting in the original study.
  
  
 
----
 
----
  
 +
==='''References'''===
  
==='''References'''===
+
<references />
  
 
Bella, J. and Rossmann, M.G. (1999) [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WM5-45GMHR3-C&_user=1111158&_coverDate=12%2F01%2F1999&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1634523500&_rerunOrigin=scholar.google&_acct=C000051676&_version=1&_urlVersion=0&_userid=1111158&md5=5726f3703771b7361a41407d5ab0e893&searchtype=a Review: Rhinoviruses and their icam receptors]. ''Journal of Structural Biology'' '''128''', 69–74.
 
Bella, J. and Rossmann, M.G. (1999) [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WM5-45GMHR3-C&_user=1111158&_coverDate=12%2F01%2F1999&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1634523500&_rerunOrigin=scholar.google&_acct=C000051676&_version=1&_urlVersion=0&_userid=1111158&md5=5726f3703771b7361a41407d5ab0e893&searchtype=a Review: Rhinoviruses and their icam receptors]. ''Journal of Structural Biology'' '''128''', 69–74.
  
Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) [http://www.jstor.org/stable/30108503 Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers]. ''Journal of Infectious Diseases'' '''125''', 243-248.
 
  
[[Category:Dose Response Model]]
+
[[Category:Dose Response Model]][[Category:Virus]][[Category:Rhinovirus]]

Latest revision as of 17:07, 15 February 2013

Rhinovirus

Author: Yin Huang


General overview

Rhinovirus, a small icosahedral viruses made of a protein capsid that encases a single-stranded, positive-sense RNA molecule, belongs to the Picornaviridae family. About 100 different serotypes have been identified and characterized by their own specific antigens.

Rhinoviruses are responsible for 30 to 50% of adult colds and 10 to 25% of colds in children. Other cold-causing viruses are adenoviruses, coronaviruses, coxsackieviruses, echoviruses, orthomyxoviruses, paramyxoviruses, respiratory syncytial virus, and enteroviruses, each of which produces infections with slightly different patterns of symptoms and severity. Several of the above-mentioned viruses also account for other more severe illnesses (Bella and Rossmann 1999).




Summary Data

Hendley et al. (1972) inoculated young adult human volunteers over the age of 21 with Rhinovirus type 39 (RV 39), strain SF 299, and rhinovirus type 14 (RV 14), strain SF 765, via intranasal exposure route. Shedding of the challenge virus and/or a fourfold or greater increase in titer of serum antibody to a homotypic rhinovirus were accepted as evidence of infection.


Experiment serial number Reference Host type Agent strain Route # of doses Dose units Response Best fit model Optimized parameter(s) LD50/ID50
65* [1] human type 39 intranasal 6 TCID50 doses infection beta-Poisson α = 2.21E-01 , N50 = 1.81E+00 1.81E+00
64 [1] human type 14 intranasal 6 TCID50 doses infection beta-Poisson α = 2.01E-01 , N50 = 9.22E+00 9.22E+00
310 [1] human type 14 intranasal 6 TCID50 doses infection beta-Poisson α = 2.52E-01 , N50 = 3.83E+00 3.83E+00
311 [1] human type 39 intranasal 6 TCID50 doses infection beta-Poisson α = 7.01E-01 , N50 = 1.9E-01 1.9E-01
312 [1] human type 14 intranasal 6 TCID50 doses infection beta-Poisson α = 1.81E-01 , N50 = 2.22E+01 2.22E+01
313 [1] human type 39 intranasal 6 TCID50 doses infection beta-Poisson α = 2E-01 , N50 = 1.05E+01 1.05E+01
312, 313 [1] human type 14 intranasal 12 TCID50 doses infection beta-Poisson α = 1.82E-01 , N50 = 1.38E+01 1.38E+01
*This model is preferred in most circumstances. However, consider all available models to decide which one is most appropriate for your analysis.
Exponential and betapoisson model.jpg

Optimization Output for experiment 65

human/type 39 strain SF 299 model data [1]
Dose Infected Non-infected Total
0.05 0 11 11
0.15 2 7 9
0.5 8 16 24
5 5 11 16
50 47 15 62


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 50.3 44.3 4 3.84
2.76e-11
9.49
3.06e-10
Beta Poisson 6.01 3 7.81
0.111
Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.


Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
α 2.24E-01 9.88E-04 1.40E-01 1.53E-01 3.71E-01 4.27E-01 7.63E-01
N50 3.29E+00 1.90E-02 1.34E+00 1.59E+00 7.67E+00 9.27E+00 1.59E+01


Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
beta Poisson model plot, with confidence bounds around optimized model



Optimization Output for experiment 64

human/type 14 strain SF 765model data [1]
Dose Infected Non-infected Total
0.5 1 8 9
1.5 4 6 10
5 4 6 10
15 6 4 10
150 27 13 40
300 10 2 12


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 51.8 50.2 5 3.84
1.42e-12
11.1
5.8e-10
Beta Poisson 1.68 4 9.49
0.794
Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.


Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
α 2.01E-01 7.76E-02 1.07E-01 1.22E-01 3.36E-01 3.69E-01 4.61E-01
N50 9.22E+00 1.41E+00 2.57E+00 3.40E+00 2.47E+01 3.14E+01 5.26E+01


Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
beta Poisson model plot, with confidence bounds around optimized model



Optimization Output for experiment 310

TITLE [1]
Dose INFECTION NOT

INFECTION || Total

0.5 1 4 5
1.5 2 3 5
5 3 2 5
15 2 1 3
150 14 5 19
300 5 0 5
Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 29.7 27.3 5 3.84
{{{pbPbetter}}}
11.1
1.71e-05
Beta Poisson 2.42 4 9.49
0

selection

Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.
Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
α 2.52E-01 9.79E-04 9.14E-02 1.16E-01 5.50E-01 6.41E-01 1.06E+00
N50 3.83E+00 9.08E-03 3.23E-01 6.41E-01 1.48E+01 2.04E+01 8.86E+01
Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
beta Poisson model plot, with confidence bounds around optimized model



Optimization Output for experiment 311

TITLE [1]
Dose INFECTION NOT

INFECTION || Total

0.05 0 2 2
0.15 1 3 4
0.5 5 2 7
1.5 18 1 19
5 1 0 1
50 19 1 20
Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 61.7 56.8 5 3.84
{{{pbPbetter}}}
11.1
5.32e-12
Beta Poisson 4.95 4 9.49
0

selection

Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.
Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
α 7.01E-01 2.29E-01 3.14E-01 3.63E-01 1.81E+06 3.82E+06 1.41E+07
N50 1.9E-01 2.27E-02 5.85E-02 7.93E-02 4.20E-01 4.52E-01 5.56E-01
Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
beta Poisson model plot, with confidence bounds around optimized model



Optimization Output for experiment 312

TITLE [1]
Dose INFECTION NOT

INFECTION || Total

0.5 0 4 4
1.5 2 3 5
5 1 4 5
15 4 3 7
150 13 8 21
300 5 2 7
Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 24.3 21.5 5 3.84
{{{pbPbetter}}}
11.1
0.000194
Beta Poisson 2.77 4 9.49
0

selection

Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.
Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
α 1.81E-01 3.92E-02 7.30E-02 9.02E-02 4.00E-01 4.79E-01 7.28E-01
N50 2.22E+01 3.12E+00 5.01E+00 6.38E+00 1.22E+02 2.06E+02 1.26E+03
Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
beta Poisson model plot, with confidence bounds around optimized model



Optimization Output for experiment 313

TITLE [1]
Dose INFECTION NOT

INFECTION || Total

0.05 0 4 4
0.15 1 4 5
0.5 3 14 17
1.5 4 10 14
5 4 11 15
50 28 14 42
Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 29.2 26.2 5 3.84
{{{pbPbetter}}}
11.1
2.16e-05
Beta Poisson 2.93 4 9.49
0

selection

Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.
Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
α 2E-01 7.86E-02 9.79E-02 1.11E-01 4.65E-01 5.58E-01 8.66E-01
N50 1.05E+01 3.00E+00 3.98E+00 4.65E+00 3.67E+01 5.32E+01 1.22E+02
Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
beta Poisson model plot, with confidence bounds around optimized model



Optimization Output for pooled experiments of 312&313

TITLE [1]
Dose INFECTION NOT

INFECTION || Total

0.05 0 4 4
0.15 1 4 5
0.5 0 4 4
0.5 3 14 17
1.5 2 3 5
1.5 4 10 14
5 1 4 5
5 4 11 15
15 4 3 7
50 28 14 42
150 13 8 21
300 5 2 7
"
Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 78.6 72.3 11 3.84
{{{pbPbetter}}}
19.7
2.8e-12
Beta Poisson 6.22 10 18.3
0.796
{{{interpretation}}}
"
Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
α 1.82E-01 1.04E-03 1.03E-01 1.14E-01 3.04E-01 3.38E-01 4.09E-01
N50 1.38E+01 2.98E+00 5.64E+00 6.67E+00 3.77E+01 4.98E+01 1.32E+02
Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
beta Poisson model plot, with confidence bounds around optimized model


Summary

The responses caused by doses less than one observed in these two experiments are probably due to the uncertainties of dose counting in the original study.



References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 Hendley, J.O., Edmondson Jr., W.P. and Gwaltney Jr., J.M. (1972) Relation between naturally acquired immunity and infectivity of two rhinoviruses involunteers. Journal of Infectious Diseases 125, 243-248. Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hendley_et_al..2C_1972" defined multiple times with different content

Bella, J. and Rossmann, M.G. (1999) Review: Rhinoviruses and their icam receptors. Journal of Structural Biology 128, 69–74.