Table 2.

Human malaria studies that have employed systems-based approaches

Study	Year	Plasmodium species	Comparison groups	Study design	Immune status	Age	Primary platform
Arévalo-Herrera et al.36	2016	Plasmodium vivax	asymptomatic infection and uncomplicated malaria	CHMI	naïve or semi-immune	adults	protein microarrays
Bediako et al.37	2019	Plasmodium falciparum	high and low prior malaria exposure	prospective cohort	semi-immune	children	RNA-seq transcriptomics
Boldt et al.38	2019	Plasmodium falciparum	asymptomatic infection, uncomplicated malaria, severe malarial anemia, and cerebral malaria	cross-sectional	semi-immune	children	microarray transcriptomics
Chakraborty et al.39	2018	Plasmodium falciparum and Plasmodum vivax	severe and uncomplicated malaria	cross-sectional	semi-immune	adults	microarray transcriptomics
Chakravorty et al.40	2007	Plasmodium falciparum	in vitro co-culture of human umbilical vein endothelial cells with P. falciparum infected erythrocytes and uninfected erythrocytes	in vitro culture	naïve	not applicable	microarray transcriptomics
Chattopadhyay et al.41	2011	Plasmodium falciparum	in vitro P. falciparum sporozoite infected and non-infected HepG2-A16 liver cells	in vitro culture	not applicable	not applicable	microarray transcriptomics
Chen et al.42	2010	Plasmodium vivax	uncomplicated malaria	cross-sectional	semi-immune	adults	protein microarrays
Chen et al.43	2015	Plasmodium vivax	P. vivax exposed	cross-sectional	naïve or semi-immune	adults	protein microarrays
Colborn et al.44	2015	Plasmodium falciparum	uncomplicated malaria	cross-sectional	semi-immune	children	microarray transcriptomics
Cordy et al.45	2019	Plasmodium coatneyi and Plasmodium falciparum	uncomplicated malaria and chronic Plasmodium infection	cross-sectional	semi-immune	adults	plasma metabolomics in macaques with validation in humans
Crompton et al.46	2010	Plasmodium falciparum	malaria exposed	prospective cohort	semi-immune	children and adults	protein microarrays
Dent et al.47	2015	Plasmodium falciparum	malaria exposed	prospective cohort	semi-immune	children and adults	protein microarrays
Dobbs et al.48	2017	Plasmodium falciparum	uncomplicated malaria, convalescent malaria, and asymptomatic P. falciparum infection	longitudinal analysis	semi-immune	children	microarray transcriptomics
Doolan et al.49	2008	Plasmodium falciparum	volunteers immunized with radiation-attenuated P. falciparum sporozoites and naturally exposed donors	longitudinal analysis (vaccine study) and cross-sectional (natural malaria exposure)	previously malaria-naïve or semi-immune	children and adults	protein microarrays
Dunache et al.50	2015	Plasmodium falciparum	antigen-stimulated PBMCs from volunteers in either RTS,S/AS02A and thrombospondin-related adhesive protein (TRAP) malaria vaccine trials	vaccination and CHMI	previously malaria-naïve	adults	microarray transcriptomics
Feintuch et al. 51	2016	Plasmodium falciparum	retinopathy-positive and retinopathy-negative cerebral malaria	cross-sectional	semi-immune	children	microarray transcriptomics
Felgner et al.52	2013	Plasmodium falciparum	uncomplicated malaria	CHMI and natural infection	naïve or semi-immune	adults	protein microarrays
Franklin et al.53	2009	Plasmodium falciparum	uncomplicated malaria	cross-sectional	semi-immune	adults	microarray transcriptomics
Gardinassi et al.54	2018	Plasmodium vivax	pre-symptomatic and uncomplicated malaria	CHMI	naïve or semi-immune	adults	integrated metabolomics and transcriptomics
Grangeiro de Carvalho et al.55	2011	Plasmodium falciparum	in vitro co-culture of NK cells with P. falciparum infected erythrocytes and uninfected erythrocytes	in vitro co-culture	naïve	adults	microarray transcriptomics
Grangeiro de Carvalho et al.56	2011	Plasmodium falciparum	in vitro co-culture of NK92 cells cells with P. falciparum infected erythrocytes and uninfected erythrocytes	in vitro co-culture	naïve	adults	microarray transcriptomics
Idaghdour et al.57	2012	Plasmodium falciparum	uncomplicated malaria	case-control	semi-immune	children	Integrated transcriptomics and genomics
Kamuyu et al.58	2018	Plasmodium falciparum	malaria-exposed and malaria-naïve	cross-sectional	naïve or semi-immune	adults	protein microarrays
Kassa et al.59	2011	Plasmodium falciparum	uncomplicated malaria and severe malaria	cross-sectional	semi-immune	adults	metabolomics
Kazmin et al.60	2017	Plasmodium falciparum	volunteers immunized with RTS,S (RRR) and RTS,S/AS01 following a primary immunization with adenovirus 35 (Ad35) vector expressing circumsporozoite protein (ARR)	vaccination and CHMI	naïve	adults	microarray transcriptomics
Keller et al.61	2009	Plasmodium falciparum	in vitro culture of PBMCs from malaria-exposed and malaria-naïve donors with and without P. falciparum hemozoin	in vitro co-culture	naïve or semi-immune	children and adults	microarray transcriptomics
Krupka et al.62	2012	Plasmodium falciparum	uncomplicated malaria and severe malaria	longitudinal analysis	semi-immune	children	microarray transcriptomics
Kumar et al.63	2018	Plasmodium falciparum	cerebral malaria	case-control	semi-immune	children and adults	proteomics of frontal lobe samples
Lee et al.64	2018	Plasmodium falciparum	uncomplicated malaria and severe malaria	cross-sectional	semi-immune	children	whole-blood RNA-seq transcriptomics
Leopold et al.65	2019	Plasmodium falciparum	uncomplicated malaria and severe malaria	nested case-control	semi-immune	adults	plasma metabolomics with in vitro validation
Lu et al.66	2014	Plasmodium vivax	uncomplicated malaria	cross-sectional	naïve or semi-immune	adults	protein microarrays
Nallandhighal et al.67	2019	Plasmodium falciparum	cerebral malaria, severe malarial anemia, malaria exposed community controls	nested case-control	semi-immune	children	microarray transcriptomics with plasma biomarkers
Nnedu et al.68	2011	Plasmodium falciparum	malaria exposed with HIV co-infection	cross-sectional	semi-immune	adults	protein microarrays
Ockenhouse et al.69	2006	Plasmodium falciparum	pre-symptomatic infection and uncomplicated malaria	CHMI and natural infection	naïve or semi-immune	adults	microarray transcriptomics
Orikiiriza et al.70	2017	Plasmodium falciparum	uncomplicated malaria and severe malaria	cross-sectional	semi-immune	children	lipidomics
Portugal et al.71	2014	Plasmodium falciparum	in vitro co-culture of PBMCs with P. falciparum infected erythrocytes and uninfected erythrocytes	longitudinal analysis	semi-immune	children	microarray transcriptomics
Quin et al.72	2017	Plasmodium falciparum	malaria exposed	cross-sectional	semi-immune	adults	RNA-seq transcriptomics and genome-wide DNA methylation
Ray et al.73	2012	Plasmodium falciparum and Plasmodium vivax	uncomplicated malaria	cross-sectional	semi-immune	adults	proteomics
Ray et al.74	2012	Plasmodium vivax	uncomplicated malaria	cross-sectional	naïve or semi-immune	adults	proteomics
Ray et al.75	2015	Plasmodium falciparum	uncomplicated malaria and severe malaria	cross-sectional	semi-immune	adults	proteomics
Reuterswärd et al.76	2018	Plasmodium falciparum	uncomplicated malaria and severe malaria	case-control	semi-immune	children	proteomics
Rojas-Peña et al.77	2015	Plasmodium vivax	uncomplicated malaria	case-control	naïve or semi-immune	adults	quantitative RT-PCR array and RNA-seq transcriptomics
Rojas-Peña et al.78	2018	Plasmodium falciparum and Plasmodum vivax	malaria exposed	longitudinal analysis	semi-immune	adults	RNA-seq transcriptomics
Rothen et al.79	2018	Plasmodium falciparum	pre-symptomatic infection and uncomplicated malaria	CHMI	semi-immune	adults	RNA-seq transcriptomics
Torres et al.80	2015	Plasmodium falciparum	uncomplicated malaria and asymptomatic infection	cross-sectional	naïve or semi-immune	adults	protein microarrays
Tran et al.81	2016	Plasmodium falciparum	uncomplicated malaria and asymptomatic infection	CHMI and natural infection	naïve or semi-immune	adults	RNA-seq transcriptomics
Tran et al.82	2019	Plasmodium falciparum	volunteers immunized with sporozoites under chemoprophylaxis (CPS)	vaccination and CHMI	naïve	adults	RNA-seq transcriptomics
Tran et al.83	2019	Plasmodium falciparum	asymptomatic infection and uncomplicated malaria	nested case-control in a prospective study	semi-immune	children	RNA-seq transcriptomics
Tripathi et al.84	2009	Plasmodium falciparum	in vitro co-culture of human brain microvascular endothelial cells with P. falciparum infected erythrocytes and uninfected erythrocytes	in vitro co-culture	naïve	not applicable	microarray transcriptomics
Uplekar et al.85	2017	Plasmodium falciparum and Plasmodum vivax	asymptomatic infection, uncomplicated malaria	cross-sectional	semi-immune	adults	protein microarrays
Vahey et al.86	2010	Plasmodium falciparum	volunteers immunized with the RTS,S malaria vaccine	vaccination and CHMI	previously malaria-naïve	adults	microarray transcriptomics
Vallejo et al.87	2018	Plasmodium vivax	pre-symptomatic and uncomplicated malaria	CHMI	naïve or semi-immune	adults	RNA-seq transcriptomics
van den Berg et al.88	2017	Plasmodium falciparum	volunteers immunized with the RTS,S malaria vaccine	vaccination and CHMI	naïve	adults	microarray transcriptomics
Yamagishi et al.89	2014	Plasmodium falciparum	uncomplicated malaria	cross-sectional	semi-immune	children and adults	RNA-seq transcriptomics