Summary of Study ST001384
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000948. The data can be accessed directly via it's Project DOI: 10.21228/M8540T This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST001384 |
| Study Title | Plasmodium falciparum increased time in circulation underlies persistent asymptomatic infection in the dry season |
| Study Summary | The dry season is a major challenge for Plasmodium falciparum parasites in many malaria endemic regions, where water availability limits mosquitoes to only part of the year. How P. falciparum bridges two transmission seasons months apart, without being cleared by the host or compromising host survival is poorly understood. Here we show that low levels of P. falciparum parasites persist in the blood of asymptomatic Malian individuals during the 5- to 6-month dry season, rarely causing symptoms and minimally affecting the host immune response. Parasites isolated during the dry season are transcriptionally distinct from those of subjects with febrile malaria in the transmission season, reflecting longer circulation within each replicative cycle, of parasitized erythrocytes without adhering to the vascular endothelium. Low parasite levels during the dry season are not due to impaired replication, but rather increased splenic clearance of longer-circulating infected erythrocytes. We propose that P. falciparum virulence in areas of seasonal malaria transmission is regulated so that the parasite decreases its endothelial binding capacity, allowing increased splenic clearance and enabling several months of subclinical parasite persistence. |
| Institute | Pennsylvania State University |
| Last Name | Llinas |
| First Name | Manuel |
| Address | W126 Millennium Science Complex, University Park, PENNSYLVANIA, 16802, USA |
| manuel@psu.edu | |
| Phone | (814) 867-3527 |
| Submit Date | 2020-05-25 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2020-08-20 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR000948 |
| Project DOI: | doi: 10.21228/M8540T |
| Project Title: | Plasmodium falciparum increased time in circulation underlies persistent asymptomatic infection in the dry season |
| Project Summary: | The dry season is a major challenge for Plasmodium falciparum parasites in many malaria endemic regions, where water availability limits mosquitoes to only part of the year. How P. falciparum bridges two transmission seasons months apart, without being cleared by the host or compromising host survival is poorly understood. Here we show that low levels of P. falciparum parasites persist in the blood of asymptomatic Malian individuals during the 5- to 6-month dry season, rarely causing symptoms and minimally affecting the host immune response. Parasites isolated during the dry season are transcriptionally distinct from those of subjects with febrile malaria in the transmission season, reflecting longer circulation within each replicative cycle, of parasitized erythrocytes without adhering to the vascular endothelium. Low parasite levels during the dry season are not due to impaired replication, but rather increased splenic clearance of longer-circulating infected erythrocytes. We propose that P. falciparum virulence in areas of seasonal malaria transmission is regulated so that the parasite decreases its endothelial binding capacity, allowing increased splenic clearance and enabling several months of subclinical parasite persistence. |
| Institute: | Pennsylvania State University |
| Last Name: | Llinas |
| First Name: | Manuel |
| Address: | W126 Millennium Science Complex, University Park, PENNSYLVANIA, 16802, USA |
| Email: | manuel@psu.edu |
| Phone: | (814) 867-3527 |
Subject:
| Subject ID: | SU001458 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype |
|---|---|---|
| SA101065 | blank1 | Blank |
| SA101066 | blank3 | Blank |
| SA101067 | blank2 | Blank |
| SA101068 | blank4 | Blank |
| SA101069 | b332 | MAL |
| SA101070 | b322 | MAL |
| SA101071 | b262 | MAL |
| SA101072 | b385 | MAL |
| SA101073 | b459 | MAL |
| SA101074 | b224 | MAL |
| SA101075 | b443 | MAL |
| SA101076 | b400 | MAL |
| SA101077 | b391 | MAL |
| SA101078 | b371 | MAL |
| SA101079 | b170 | MAL |
| SA101080 | b161 | MAL |
| SA101081 | poolb1 | MAL Pool |
| SA101082 | poolb2 | MAL Pool |
| SA101083 | poolb3 | MAL Pool |
| SA101084 | a320 | May |
| SA101085 | a326 | May |
| SA101086 | a325 | May |
| SA101087 | a308 | May |
| SA101088 | a351 | May |
| SA101089 | a244 | May |
| SA101090 | a448 | May |
| SA101091 | a388 | May |
| SA101092 | a373 | May |
| SA101093 | a355 | May |
| SA101094 | a357 | May |
| SA101095 | a334 | May |
| SA101096 | poola3 | May Pool |
| SA101097 | poola1 | May Pool |
| SA101098 | poola2 | May Pool |
| SA101099 | qc1 | Pool |
| SA101100 | qc2 | Pool |
| SA101101 | qc3 | Pool |
| Showing results 1 to 37 of 37 |
Collection:
| Collection ID: | CO001453 |
| Collection Summary: | 2 mL venous blood was drawn of RDT+ individuals tested at the end of the dry season (May 2012) cross-sectional, and at the first malaria episode of the ensuing transmission season, into EDTA tubes (Vacutainer K3EDTA Tubes, BD) and processed directly at the field site. Plasma (used for metabolomic analysis) was separated by centrifugation and immediately frozen in liquid N2. Buffy coat was discarded and the RBC pellet was further removed of leucocytes in a two-step procedure; first by density gradient on Lymphoprep solution (Fresenius Kabi), followed by Plasmodipur (EuroProxima) filtration. |
| Sample Type: | Blood (plasma) |
Treatment:
| Treatment ID: | TR001473 |
| Treatment Summary: | None, samples were collected at 2 natural timepoints. RDT+ individuals tested at the end of the dry season (May 2012) cross-sectional, and at the first malaria episode of the ensuing transmission season. |
Sample Preparation:
| Sampleprep ID: | SP001466 |
| Sampleprep Summary: | Each plasma sample was split into two independent samples for metabolite extraction. For hydrophilic metabolites, 50µL of plasma was extracted by the addition of 9X volumes of ice cold methanol. Samples were briefly vortexed before centrifuging for 10 minutes to remove precipitated protein. The clarified supernatants were dried under nitrogen gas and resuspended in 100µL (1:2 dilution final). For hydrophobic metabolites, 25µL of plasma was extracted by the addition of 3X volumes of isopropanol. Samples were briefly vortexed and allowed to sit at room temperature for 10 minutes. Samples were then placed at -20 °C to precipitate overnight. Precipitated samples were centrifuged for 20 minutes and the clarified supernatant was diluted to 50% water in a glass LCMS sample vial (1:6 dilution final). Sample groups were pooled to create a group QA and all samples were pooled to create a batch QC, which were injected periodically throughout each run. |
Combined analysis:
| Analysis ID | AN002308 | AN002309 | AN002310 | AN002311 |
|---|---|---|---|---|
| Analysis type | MS | MS | MS | MS |
| Chromatography type | Reversed phase | Reversed phase | Reversed phase | Reversed phase |
| Chromatography system | Shimadzu Prominence 20 UFLCXR | Thermo Dionex Ultimate 3000 | Shimadzu Prominence 20 UFLCXR | Shimadzu Prominence 20 UFLCXR |
| Column | Waters BEH C18 (100mm x 2.1mm; 1.7um) | Waters XSelect HSS T3 (100 x 2.1mm,2.5um) | Waters Acquity CSH C18 (100 x 2.1mm,1.7um) | Waters Acquity CSH C18 (100 x 2.1mm,1.7um) |
| MS Type | ESI | ESI | ESI | ESI |
| MS instrument type | Triple TOF | Orbitrap | Triple TOF | Triple TOF |
| MS instrument name | ABI Sciex 5600 TripleTOF | Thermo Exactive Plus Orbitrap | ABI Sciex 5600 TripleTOF | ABI Sciex 5600 TripleTOF |
| Ion Mode | POSITIVE | NEGATIVE | POSITIVE | NEGATIVE |
| Units | Area | Area | Area |
Chromatography:
| Chromatography ID: | CH001695 |
| Instrument Name: | Shimadzu Prominence 20 UFLCXR |
| Column Name: | Waters BEH C18 (100mm x 2.1mm; 1.7um) |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH001696 |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Waters XSelect HSS T3 (100 x 2.1mm,2.5um) |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH001697 |
| Instrument Name: | Shimadzu Prominence 20 UFLCXR |
| Column Name: | Waters Acquity CSH C18 (100 x 2.1mm,1.7um) |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH001698 |
| Instrument Name: | Shimadzu Prominence 20 UFLCXR |
| Column Name: | Waters Acquity CSH C18 (100 x 2.1mm,1.7um) |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS002151 |
| Analysis ID: | AN002308 |
| Instrument Name: | ABI Sciex 5600 TripleTOF |
| Instrument Type: | Triple TOF |
| MS Type: | ESI |
| MS Comments: | The capillary voltage was set at 4.5 kV in negative ion mode, with a declustering potential of 80V. The mass spectrometer was operated in IDA (Information Dependent Acquisition) mode with a 100 ms survey scan from 100 to 1200 m/z, and up to 20 MS/MS product ion scans (100 ms) per duty cycle using a collision energy of 50V with a 20V spread. Data processing was performed using MS-DIAL and annotated using the built-in public library. Blank subtraction and analysis was performed in excel. |
| Ion Mode: | POSITIVE |
| MS ID: | MS002152 |
| Analysis ID: | AN002309 |
| Instrument Name: | Thermo Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Aquired in MS1 mode only. Data processing and annotation performed using MAVEN and an in-house targeted list. Blank subtraction and analysis was performed in excel. |
| Ion Mode: | NEGATIVE |
| MS ID: | MS002153 |
| Analysis ID: | AN002310 |
| Instrument Name: | ABI Sciex 5600 TripleTOF |
| Instrument Type: | Triple TOF |
| MS Type: | ESI |
| MS Comments: | IDA MS2 method. Ammonium formate and formic acid were added to the positive ESI solvents. Data processing performed using MS-DIAL and annotated using the in silico library. Blank subtraction and analysis was performed in excel. |
| Ion Mode: | POSITIVE |
| MS ID: | MS002154 |
| Analysis ID: | AN002311 |
| Instrument Name: | ABI Sciex 5600 TripleTOF |
| Instrument Type: | Triple TOF |
| MS Type: | ESI |
| MS Comments: | IDA MS2 method. Ammonium acetate was used for negative ESI solvents. Data processing performed using MS-DIAL and annotated using the in silico library. Blank subtraction and analysis was performed in excel. |
| Ion Mode: | NEGATIVE |
