In this document we keep track of the exercise of going through the datasets.
Install packages described in /African-genetics/malaria-infect/src/branch/master/README.md
Learning R and loading data
Read 'R for Data Science'
Read 'Discovering Statistics with R
Set current working directory in http://git.genenetwork.org/African-genetics/malaria-infect/src/branch/master/doc/02-load-data.Rmd#L13
Some data attributes and simple plot in http://git.genenetwork.org/African-genetics/malaria-infect/src/branch/master/doc/02-load-data.Rmd#L62
Output in 02-load-data.html
Start using Tidyverse
Output in 03-using-tidyverse.html
Assess new dataset with covariates
Schizont/ELISA vs time to diagnosis, see https://biogems.info/KEMRI/Malaria/03-using-tidyverse.html
Merge cytokines with covariates
Explore cytokines responses with groups
Francis Ndungu & Pjotr Prins
SampleID – Volunteer enrolment number
Age – Age at time of trial (years)
Gender – Participant’s gender (1 = male, 0 = female)
Location – Location of normal residence
ELISA – Titre or anti-schizont antibody at screening (relative ELISA units)
ELISA maps to Schizont column (log10 transformed)
anti-schizont antibody is measured before infection
Lumefantrine log10 too. Lumefantrine is an antimalarial drug. It is only used in combination with artemether. The term "co-artemether" is sometimes used to describe this combination. Lumefantrine has a much longer half-life compared to artemether, and is therefore thought to clear any residual parasites that remain after combination treatment.
Treg_freq – The frequency of Tregs as a proportion of CD4+ T cells
Treg_Ki67_FC – The fold change in the number of Tregs expressing Ki-67 (a proliferation marker) between C-1 and C+14
Treg_CD45RA – The proportion of Tregs expressing CD45RA (naïve T cell marker)
Teff_Ki67_FC – The fold change in the number of Teffs expressing Ki-67 (a proliferation marker) between C-1 and C+14
Teff_CD45RA – The proportion of Tregs expressing CD45RA (naïve T cell marker)
Cytokine_status_cm1 – Detectable level of pro-inflammatory cytokines at C-1 (1 = yes, 0 = no)
Screening PCR – Whether the volunteer had detectable parasitaemia at screening by qPCR (1 = yes, 0 = no)
Symptoms_DoD – (Treated group only) whether the volunteer was symptomatic (indicated by raise in temperature) at the day of diagnosis (1 = yes, 0 = no)
IL10_cm1 – Whether the volunteer had detectable IL-10 at C-1 (1 = yes, 0 = no)
IL10_DoD – Whether the volunteer had detectable IL-10 at the day of Diagnosis (1 = yes, 0 = no)
Cytokines are a broad and loose category of small proteins (~5–20 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. A given cytokine may be produced by more than one type of cell. They act through cell surface receptors and are especially important in the immune system; cytokines modulate the balance between humoral and cell-based immune responses.
For malaria the relative balance between Th1 and Th2 cytokines appears crucial. Th1 cytokines, interleukin-12 (IL-12) and gamma interferon (IFN-γ), and anti-inflammatory Th2 cytokines, IL-4 and IL-10 play a role.
Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. In humans, interleukin 10 is encoded by the IL10 gene. IL-10 downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. IL-10 can block NF-κB activity, and is involved in the regulation of the JAK-STAT signaling pathway. IL-10 counteracts the hyperactive immune response in the human body.
The T helper cells (Th cells), also known as CD4+ cells, are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. They help the activity of other immune cells by releasing T cell cytokines. These cells help suppress or regulate immune responses.
The regulatory T cells (Tregs ˈtiːrɛɡ or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Tregs are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells.