Table 1.

Methodologies and tools commonly used in published systems studies of malaria immunity in humans

Objective	Methodology or Tool	Applicable to	Reference(s)
Determine differences between phenotypes or groups	Cufflinks/Cuffdiff	RNA-seq	Trapnell et al. 201210
	DESeq2	RNA-seq	Love et al. 201411
	edgeR	RNA-seq	Robinson et al. 201012
	empirical Bayes moderated t test (limma)	microarrays	Ritchie et al. 201513
	Power Law Global Error Model (PLGEM)	microarrays	Pavelka 200414
	significance analysis of microarrays (SAM)	microarrays	Tusher 200115
	voom-limma	RNA-seq	Ritchie et al 201513
Deconvolution of transcriptomic data from heterogeneous tissue	Immune Response in Silico (IRIS)	transcriptomic datasets	Abbas et al. 200916
	immunoStates	transcriptomic datasets	Vallania et al. 201817
	leukocyte signature matrix (LM22; CIBERSORT)	transcriptomic datasets	Newman et al. 201518
Functional and pathways analysis	Camera	molecular -omic datasets	Wu and Smyth 201219
	DAVID functional annotation	molecular -omic datasets	Huang et al. 200720,21
	Gene set enrichment analysis	molecular -omic datasets	Subramanian et al. 200522
	Ingenuity (for pathways analysis; proprietary)	molecular -omic datasets	Kramer et al. 2014 23
	Coincident extreme ranks in numerical observations (CERNO; implemented via tmod)	molecular -omic datasets	Zyla et al. 201924
Gene Correlation Network analysis	weighted gene co-expression network analysis (WGCNA)	molecular -omic datasets	Langfelder and Horvath 200825
Integrative analysis with Plasmodium genome or proteome; protein arrays for antibody profiling	PlasmoDB Plasmodium genomics resource	Plasmodium -omic datasets	Aurrecoechea et al. 200926
Gene sets and transcriptional modules	blood transcription modules	transcriptomic datasets	Li et al. 201427
	ImmuneSigDB (C7 collection)	transcriptomic datasets	Godec et al. 201628
	Kyoto Encyclopedia of Genes and Genomes (KEGG)	molecular -omic datasets	Kanehisa and Goto 200029
	modular transcriptional repertoire	transcriptomic datasets	Chaussabel et al. 201430
	Molecular signatures database (MSigDB)	molecular -omic datasets	Liberzon et al. 201131
Platforms with accessible graphic user interfaces	DAVID Bioinformatics Resources 6.8 (https://david.ncifcrf.gov/home.jsp)	molecular -omic datasets	Huang et al. 200932
	Galaxy (https://galaxyproject.org)	molecular -omic datasets	Afgan et al. 201633
	Gene set enrichment analysis (http://software.broadinstitute.org/gsea/index.jsp)	molecular -omic datasets	Subramanian et al. 200522
	Ingenuity (for pathways analysis; proprietary)	molecular -omic datasets	Kramer et al. 2014 23
	tmod (http://tmod.online/)	transcriptomic datasets	Zyla et al. 201924