Data Analysis for Maternal-infant Vaccination

Maternal tetanus, diphtheria, and acellular pertussis (Tdap) immunization: + vs. -

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Last updated: 2024-10-16

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Knit directory: MADI-Project3-SDY8003-Thailand/

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File	Version	Author	Date	Message
Rmd	dda6b8f	f006zvn1	2024-10-16	changed index pages
html	dda6b8f	f006zvn1	2024-10-16	changed index pages
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Rmd	b797383	Michael S. Zens	2024-10-03	latest sets of feature estimates and plots.
Rmd	2ab8fdd	Michael S. Zens	2024-09-16	added feature_comparisions and fixed the deimension reduction for 6 variations of clustering for each manuscript.
Rmd	d0f0c4a	Michael S. Zens	2024-09-12	cleaned up clustering analysis codes
Rmd	30d4812	Michael S. Zens	2024-09-09	commit merge_fixed_v1
html	b2b32c1	Michael S. Zens	2024-09-09	commiting html files that I wish I could forget.
Rmd	e1a0085	Michael S. Zens	2024-09-09	msz changes for clustering and tanglegrams
html	985b979	Jie Zhou-2	2024-08-20	change the reference group
html	66f14ec	Jie Zhou-2	2024-08-20	edit the format of the results
Rmd	cd45b9e	Jie Zhou-2	2024-08-16	add boost data analysis
html	cd45b9e	Jie Zhou-2	2024-08-16	add boost data analysis
html	c354391	Jie Zhou-2	2024-08-16	ignore file
html	184e4fb	Jie Zhou-2	2024-08-16	knit index file
Rmd	a1b017b	Jie Zhou-2	2024-08-15	revisions on mixed effects model
html	a1b017b	Jie Zhou-2	2024-08-15	revisions on mixed effects model
html	bc8783d	Jie Zhou-2	2024-08-14	reference group to PT
Rmd	3639433	Jie Zhou-2	2024-08-14	fix a mixed effects bug
html	3639433	Jie Zhou-2	2024-08-14	fix a mixed effects bug
Rmd	a60ab45	Jie Zhou-2	2024-08-14	added mixed effects model
html	a60ab45	Jie Zhou-2	2024-08-14	added mixed effects model
html	f517c3a	Jie Zhou-2	2024-08-06	added sex to the mediation model
Rmd	fe5a646	Jie Zhou-2	2024-08-05	fix the conflicts
html	fe5a646	Jie Zhou-2	2024-08-05	fix the conflicts
Rmd	a4226da	Jie Zhou-2	2024-08-05	added vifBasedSelection.R
html	a4226da	Jie Zhou-2	2024-08-05	added vifBasedSelection.R
html	573d7bd	Kookd	2024-07-29	updating wiki docs to reflect updated umap
html	d6b37f1	Kookd	2024-07-29	updated index html files
Rmd	e0dfe6d	Kookd	2024-07-29	cluster features by arm for apwp and matim+/-, for 6 and 7 clusters. updated wiki-related documents
Rmd	6c97c29	Jie Zhou	2024-07-15	added colineary analysis
html	6c97c29	Jie Zhou	2024-07-15	added colineary analysis
html	7e05a5c	Michael S. Zens	2024-06-18	more supporting files for the Maternal Tdap+ vs. Tdap-
Rmd	ab9b91f	Michael S. Zens	2024-06-18	big set of maternal Tdap+ vs Tdap- results

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Summary:

Welcome to an analysis of infant immune response to maternal and infant immunization.

• All analyses presented on this page are for examining the difference in infants of their mothers receiving the Tdap vaccine in pregnancy.

1 Outlier and Anomaly detection by feature

1. Review assay responses and extreme values for imputation or exclusion

2. Review PCA and UMAP projection of all antigens and features by arm

2 IgG standardization

1. Check ELISA total IgG correlation with bead array MFI total IgG
2. Standardization regression - by antigen, feature and visit
3. Summary across all features - IgG Standardization - by antigen, feature and visit
4. Test across Arms by feature - unstandardized and standardized by feature and visit
5. Test Vaccinated vs. Boost - by feature - unstandardized only by feature and arm
6. JIVE Decomposition Between IgG, FcR and Effector Function Data

3 Feature Clustering

• In the Feature Clustering section, all features reflecting antibody and functional analytes binding to five antigens at the vaccinated (Month 7) and boosted (Month 19) time points are examined to determine clusters of associated features that will be response variables for the analysis.

1. Vaccinated and Boosted: unstandardized features - 7 clusters

2. Vaccinated and Boosted: standardized features by total IgG - 7 clusters

3. Vaccinated and Boosted: standardized features by total IgG - 7 clusters_no IgG

4. Vaccinated and Boosted: unstandardized features - 6 clusters

5. Vaccinated and Boosted: standardized features by total IgG - 6 clusters

6. Vaccinated and Boosted: standardized features by total IgG - 6 clusters - noIgG

7. by Arm and visit - include total IgG: not standardized - 7 clusters

8. by Arm and Visit - include total IgG: standardized - 7 clusters

9. by Arm and visit - exclude total IgG: not standardized - 7 clusters

10. by Arm and Visit - exclude total IgG: standardized - 7 clusters

11. by Arm and Visit - exclude total IgG: standardized - 6 clusters

4 Dimension Reduction and Confounding

• In the Dimension Reduction section, principle components are calculated for the pertussis related antigens (PT, FHA, PRN), other infant strains (DT, TT), and each of the Feature Clusters identified at the vaccinated and boosted time points.

  1. Table 1. Covariates associate with Study Arm

  2. Antigen & Unsupervised clusters: Not standardized - excluding ELISA total IgG - 7 clusters

  3. Antigen & Unsupervised clusters: Total IgG standardized - excluding ELISA total IgG - 7 clusters

  4. Antigen & Unsupervised clusters: Total IgG standardized - all total IgG - 7 clusters

  5. Antigen & Unsupervised clusters: Not standardized - excluding ELISA total IgG - 6 clusters

  6. Antigen & Unsupervised clusters: Total IgG standardized - excluding ELISA total IgG - 6 clusters

  7. Antigen & Unsupervised clusters: Total IgG standardized - all total IgG - 6 clusters

  8. Summary - Antigen & Unsupervised clusters associated with covariates

5 Multivariate analysis

5.1 Causal Mediation Analysis

• In the Causal Mediation Analysis section, the direct effects of the study treatments may be mediated by Cord blood (at birth) total IgG or Prevaccinated infant serum (Month 2). Response variables are of three types.

1. mediator: maternal serum, response: infant age 7 mo. (vaccinated)

5.2 Mixed-Effects model

• In this section, the infant response at month 7 is decomposed into different sources including antigen, analyte, maternal immmunization and individual effects. In particular, we focus on analyzing the interaction between maternal immunization and antigen.

1. mixed-effects model (Month 7)

2. mixed-effects model (Month 19)