CLass 18: Pertussis Mini Project

Author

Patrick Nguyen (PID:A17680785)

Background

Pertussis is a common lung infection caused by the bacteria B.Pertussis

This can infect all ages but is most severe for those under 1 year of age.

The CDC track the number of reported cases in US We can “scrape” those data with the datapasta package.

cdc <- data.frame(
                          Year = c(1922L,
                                   1923L,1924L,1925L,1926L,1927L,1928L,
                                   1929L,1930L,1931L,1932L,1933L,1934L,1935L,
                                   1936L,1937L,1938L,1939L,1940L,1941L,
                                   1942L,1943L,1944L,1945L,1946L,1947L,1948L,
                                   1949L,1950L,1951L,1952L,1953L,1954L,
                                   1955L,1956L,1957L,1958L,1959L,1960L,
                                   1961L,1962L,1963L,1964L,1965L,1966L,1967L,
                                   1968L,1969L,1970L,1971L,1972L,1973L,
                                   1974L,1975L,1976L,1977L,1978L,1979L,1980L,
                                   1981L,1982L,1983L,1984L,1985L,1986L,
                                   1987L,1988L,1989L,1990L,1991L,1992L,1993L,
                                   1994L,1995L,1996L,1997L,1998L,1999L,
                                   2000L,2001L,2002L,2003L,2004L,2005L,
                                   2006L,2007L,2008L,2009L,2010L,2011L,2012L,
                                   2013L,2014L,2015L,2016L,2017L,2018L,
                                   2019L,2020L,2021L,2022L,2023L,2024L,2025L),
  No..Reported.Pertussis.Cases = c(107473,
                                   164191,165418,152003,202210,181411,
                                   161799,197371,166914,172559,215343,179135,
                                   265269,180518,147237,214652,227319,103188,
                                   183866,222202,191383,191890,109873,
                                   133792,109860,156517,74715,69479,120718,
                                   68687,45030,37129,60886,62786,31732,28295,
                                   32148,40005,14809,11468,17749,17135,
                                   13005,6799,7717,9718,4810,3285,4249,
                                   3036,3287,1759,2402,1738,1010,2177,2063,
                                   1623,1730,1248,1895,2463,2276,3589,
                                   4195,2823,3450,4157,4570,2719,4083,6586,
                                   4617,5137,7796,6564,7405,7298,7867,
                                   7580,9771,11647,25827,25616,15632,10454,
                                   13278,16858,27550,18719,48277,28639,
                                   32971,20762,17972,18975,15609,18617,6124,
                                   2116,3044,7063,22538,21996)
)

Q. Make a plot of year vs ``cases

library(ggplot2)

ggplot(cdc) +
  aes(Year, No..Reported.Pertussis.Cases) +
  geom_point() +
  geom_line()

Q. Add some major milestones including the first wP vaccine roll-out (1946), the switch to the newer aP vaccine (1996), the COVID years (2020).

library(ggplot2)

ggplot(cdc) +
  aes(Year, No..Reported.Pertussis.Cases) +
  geom_point() +
  geom_line() +
  geom_vline(xintercept= 1946, col="blue", lty=2) +
  geom_vline(xintercept= 1996, col="red", lty=2) +
  geom_vline(xintercept= 2020, col="gray", lty=2)

After the switch to the acellular pertussis (aP) vaccine, pertussis cases began rising again, with major peaks such as the 2012 outbreak. coud be due to bacterial evolution and immunity of the vaccine.

Why is this vaccine-preventable disease on the upswing? To answer this question we need to investigate the mechanisms underlying waning protection against pertussis. This requires evaluation of pertussis-specific immune responses over time in wP and aP vaccinated individuals.

CMI-PB project

Computational Models of Immunity - Pertussis Boost project aims to provide the scientific community with this very information.

They make their data abailablke via JSON format returning API. We can read this in R with the read_json() function from the jsonlite package:

library(jsonlite)

subject <- read_json("http://cmi-pb.org/api/v5_1/subject", simplifyVector = TRUE)

head(subject)
  subject_id infancy_vac biological_sex              ethnicity  race
1          1          wP         Female Not Hispanic or Latino White
2          2          wP         Female Not Hispanic or Latino White
3          3          wP         Female                Unknown White
4          4          wP           Male Not Hispanic or Latino Asian
5          5          wP           Male Not Hispanic or Latino Asian
6          6          wP         Female Not Hispanic or Latino White
  year_of_birth date_of_boost      dataset
1    1986-01-01    2016-09-12 2020_dataset
2    1968-01-01    2019-01-28 2020_dataset
3    1983-01-01    2016-10-10 2020_dataset
4    1988-01-01    2016-08-29 2020_dataset
5    1991-01-01    2016-08-29 2020_dataset
6    1988-01-01    2016-10-10 2020_dataset

Q. How many “wP” and “aP” individuals are in the subject table?

table(subject$infancy_vac)

aP wP 
87 85 

Q. What is the biological sex breakdown?

table(subject$biological_sex)

Female   Male 
   112     60 

Q. In terms of race and gender is this dataset representative of the US population?

table(subject$race, subject$biological_sex)
                                           
                                            Female Male
  American Indian/Alaska Native                  0    1
  Asian                                         32   12
  Black or African American                      2    3
  More Than One Race                            15    4
  Native Hawaiian or Other Pacific Islander      1    1
  Unknown or Not Reported                       14    7
  White                                         48   32

Let’s read some more database tables:

specimen <- read_json( "http://cmi-pb.org/api/v5_1/specimen", simplifyVector = TRUE)

ab_titer <- read_json( "http://cmi-pb.org/api/v5_1/plasma_ab_titer", simplifyVector = TRUE)
head(specimen)
  specimen_id subject_id actual_day_relative_to_boost
1           1          1                           -3
2           2          1                            1
3           3          1                            3
4           4          1                            7
5           5          1                           11
6           6          1                           32
  planned_day_relative_to_boost specimen_type visit
1                             0         Blood     1
2                             1         Blood     2
3                             3         Blood     3
4                             7         Blood     4
5                            14         Blood     5
6                            30         Blood     6
head(ab_titer)
  specimen_id isotype is_antigen_specific antigen        MFI MFI_normalised
1           1     IgE               FALSE   Total 1110.21154       2.493425
2           1     IgE               FALSE   Total 2708.91616       2.493425
3           1     IgG                TRUE      PT   68.56614       3.736992
4           1     IgG                TRUE     PRN  332.12718       2.602350
5           1     IgG                TRUE     FHA 1887.12263      34.050956
6           1     IgE                TRUE     ACT    0.10000       1.000000
   unit lower_limit_of_detection
1 UG/ML                 2.096133
2 IU/ML                29.170000
3 IU/ML                 0.530000
4 IU/ML                 6.205949
5 IU/ML                 4.679535
6 IU/ML                 2.816431

To analyze this data we need to first “join” (merge/link) the different tables so we have all the data in one place not spread across different tables.

We can use the *_join() family of functions from dplyr to do this

library(dplyr)

Attaching package: 'dplyr'
The following objects are masked from 'package:stats':

    filter, lag
The following objects are masked from 'package:base':

    intersect, setdiff, setequal, union
meta <- inner_join(subject, specimen)
Joining with `by = join_by(subject_id)`
head(meta)
  subject_id infancy_vac biological_sex              ethnicity  race
1          1          wP         Female Not Hispanic or Latino White
2          1          wP         Female Not Hispanic or Latino White
3          1          wP         Female Not Hispanic or Latino White
4          1          wP         Female Not Hispanic or Latino White
5          1          wP         Female Not Hispanic or Latino White
6          1          wP         Female Not Hispanic or Latino White
  year_of_birth date_of_boost      dataset specimen_id
1    1986-01-01    2016-09-12 2020_dataset           1
2    1986-01-01    2016-09-12 2020_dataset           2
3    1986-01-01    2016-09-12 2020_dataset           3
4    1986-01-01    2016-09-12 2020_dataset           4
5    1986-01-01    2016-09-12 2020_dataset           5
6    1986-01-01    2016-09-12 2020_dataset           6
  actual_day_relative_to_boost planned_day_relative_to_boost specimen_type
1                           -3                             0         Blood
2                            1                             1         Blood
3                            3                             3         Blood
4                            7                             7         Blood
5                           11                            14         Blood
6                           32                            30         Blood
  visit
1     1
2     2
3     3
4     4
5     5
6     6
abdata <- inner_join(ab_titer, meta)
Joining with `by = join_by(specimen_id)`
head(abdata)
  specimen_id isotype is_antigen_specific antigen        MFI MFI_normalised
1           1     IgE               FALSE   Total 1110.21154       2.493425
2           1     IgE               FALSE   Total 2708.91616       2.493425
3           1     IgG                TRUE      PT   68.56614       3.736992
4           1     IgG                TRUE     PRN  332.12718       2.602350
5           1     IgG                TRUE     FHA 1887.12263      34.050956
6           1     IgE                TRUE     ACT    0.10000       1.000000
   unit lower_limit_of_detection subject_id infancy_vac biological_sex
1 UG/ML                 2.096133          1          wP         Female
2 IU/ML                29.170000          1          wP         Female
3 IU/ML                 0.530000          1          wP         Female
4 IU/ML                 6.205949          1          wP         Female
5 IU/ML                 4.679535          1          wP         Female
6 IU/ML                 2.816431          1          wP         Female
               ethnicity  race year_of_birth date_of_boost      dataset
1 Not Hispanic or Latino White    1986-01-01    2016-09-12 2020_dataset
2 Not Hispanic or Latino White    1986-01-01    2016-09-12 2020_dataset
3 Not Hispanic or Latino White    1986-01-01    2016-09-12 2020_dataset
4 Not Hispanic or Latino White    1986-01-01    2016-09-12 2020_dataset
5 Not Hispanic or Latino White    1986-01-01    2016-09-12 2020_dataset
6 Not Hispanic or Latino White    1986-01-01    2016-09-12 2020_dataset
  actual_day_relative_to_boost planned_day_relative_to_boost specimen_type
1                           -3                             0         Blood
2                           -3                             0         Blood
3                           -3                             0         Blood
4                           -3                             0         Blood
5                           -3                             0         Blood
6                           -3                             0         Blood
  visit
1     1
2     1
3     1
4     1
5     1
6     1

Q. What Antibody isotypes are measured for these patients?

table(abdata$isotype)

  IgE   IgG  IgG1  IgG2  IgG3  IgG4 
 6698  7265 11993 12000 12000 12000 

Q. What antigens are reported?

table(abdata$antigen)

    ACT   BETV1      DT   FELD1     FHA  FIM2/3   LOLP1     LOS Measles     OVA 
   1970    1970    6318    1970    6712    6318    1970    1970    1970    6318 
    PD1     PRN      PT     PTM   Total      TT 
   1970    6712    6712    1970     788    6318 

Let’s focus on the IgG antigen and make a plot of MFI_normalized for all anitgens.

igg <- abdata |>
  filter(isotype == "IgG")

head(igg)
  specimen_id isotype is_antigen_specific antigen        MFI MFI_normalised
1           1     IgG                TRUE      PT   68.56614       3.736992
2           1     IgG                TRUE     PRN  332.12718       2.602350
3           1     IgG                TRUE     FHA 1887.12263      34.050956
4          19     IgG                TRUE      PT   20.11607       1.096366
5          19     IgG                TRUE     PRN  976.67419       7.652635
6          19     IgG                TRUE     FHA   60.76626       1.096457
   unit lower_limit_of_detection subject_id infancy_vac biological_sex
1 IU/ML                 0.530000          1          wP         Female
2 IU/ML                 6.205949          1          wP         Female
3 IU/ML                 4.679535          1          wP         Female
4 IU/ML                 0.530000          3          wP         Female
5 IU/ML                 6.205949          3          wP         Female
6 IU/ML                 4.679535          3          wP         Female
               ethnicity  race year_of_birth date_of_boost      dataset
1 Not Hispanic or Latino White    1986-01-01    2016-09-12 2020_dataset
2 Not Hispanic or Latino White    1986-01-01    2016-09-12 2020_dataset
3 Not Hispanic or Latino White    1986-01-01    2016-09-12 2020_dataset
4                Unknown White    1983-01-01    2016-10-10 2020_dataset
5                Unknown White    1983-01-01    2016-10-10 2020_dataset
6                Unknown White    1983-01-01    2016-10-10 2020_dataset
  actual_day_relative_to_boost planned_day_relative_to_boost specimen_type
1                           -3                             0         Blood
2                           -3                             0         Blood
3                           -3                             0         Blood
4                           -3                             0         Blood
5                           -3                             0         Blood
6                           -3                             0         Blood
  visit
1     1
2     1
3     1
4     1
5     1
6     1
ggplot(igg) +
  aes(MFI_normalised, antigen) +
  geom_boxplot()

Q. Is there a difference for aP vs wP individuals with these values?

ggplot(igg) +
  aes(MFI_normalised, antigen) +
  geom_boxplot() +
  facet_wrap(~infancy_vac)

ggplot(igg) +
  aes(MFI_normalised, antigen, col=infancy_vac) +
  geom_boxplot()

Q. Is there a temprol response - i.e do valujes increase or decrease over time?

ggplot(igg) +
  aes(MFI_normalised, antigen, col=infancy_vac) +
  geom_boxplot() +
  facet_wrap(~visit)

Focus on “PT” Pertusisis toxin antigen

pt.igg.21 <- igg |> filter(antigen == "PT",
              dataset== "2021_dataset")
ggplot(pt.igg.21) +
  aes(planned_day_relative_to_boost, MFI_normalised, col=infancy_vac, group = subject_id) +
  geom_point() +
  geom_line() +
  geom_vline(xintercept = 14, lty=2)

Final Graph

ggplot(pt.igg.21) +
  aes(planned_day_relative_to_boost, MFI_normalised, col=infancy_vac, group = subject_id) +
  geom_point() +
  geom_line() +
  geom_vline(xintercept = 14, lty=2) +
  geom_vline(xintercept = 0, lty=2) +
  labs(
    title = "CMI-PB 2021 dataset IgG PT",
    subtitle = "Dashed lines at day 0 (pre boost) and day 14 (post boost)",
    x = "Day relative to boost",
    y = "Normalised MFI"
  ) +
  geom_smooth(aes(x = planned_day_relative_to_boost, y = MFI_normalised, group = infancy_vac), se= FALSE, , size = 1.5, span = .3)
Warning: Using `size` aesthetic for lines was deprecated in ggplot2 3.4.0.
ℹ Please use `linewidth` instead.
Warning in simpleLoess(y, x, w, span, degree = degree, parametric = parametric,
: pseudoinverse used at -0.6
Warning in simpleLoess(y, x, w, span, degree = degree, parametric = parametric,
: neighborhood radius 3.6
Warning in simpleLoess(y, x, w, span, degree = degree, parametric = parametric,
: reciprocal condition number 0
Warning in simpleLoess(y, x, w, span, degree = degree, parametric = parametric,
: There are other near singularities as well. 11364
Warning in simpleLoess(y, x, w, span, degree = degree, parametric = parametric,
: pseudoinverse used at -0.6
Warning in simpleLoess(y, x, w, span, degree = degree, parametric = parametric,
: neighborhood radius 3.6
Warning in simpleLoess(y, x, w, span, degree = degree, parametric = parametric,
: reciprocal condition number 2.4057e-16
Warning in simpleLoess(y, x, w, span, degree = degree, parametric = parametric,
: There are other near singularities as well. 11364