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5. Alternative modes of tyrosyl phosphopeptide binding to a Src family SH2 domain: implications for regulation of tyrosine kinase activity

Author

Ladbury John E., Hensmann, Meike, Panayotou, George, and Campbell, Iain D.

Subjects
Phosphoproteins -- Analysis, Ligand binding (Biochemistry) -- Research, Protein tyrosine kinase -- Analysis, Tyrosine -- Analysis, Cellular signal transduction -- Physiological aspects, Biological sciences, Chemistry
Abstract

The binding mechanism of two tyrosyl phosphopeptides with the SH2 domain of the Src family was analyzed by nuclear magnetic resonance. The insertion of pY side chain to a pocket during the binding of the peptides contributes to the total free energy needed for the formation of the complex. A network of hydrogen bonds between phosphotyrosine and the SH2 domain was detected in the SH2-pY-peptide complexes. The free-energy of binding for the complex was enhanced by the contact of the isoleucine side chain with several hydrophobic residues.

Published
1996

7. Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer MG, Corran, Patrick, Risley, Paul, Silva, Nilupa, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Clark, Taane G, Band, Gavin, Clarke, Geraldine M, Spencer, Christopher CA, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Ly, Alioune Badara, Mercereau-Puijalon, Odile, Sakuntabhai, Anavaj, Djimdé, Abdoulaye, Maiga, Boubacar, Touré, Ousmane, Doumbo, Ogobara K, Dolo, Amagana, Troye-Blomberg, Marita, Mangano, Valentina D, Verra, Frederica, Modiano, David, Bougouma, Edith, Sirima, Sodiomon B, Ibrahim, Muntaser, Hussain, Ayman, Eid, Nahid, Elzein, Abier, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas N, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Manjurano, Alphaxard, Reyburn, Hugh, Lemnge, Martha, Ishengoma, Deus, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Dewasurendra, Rajika, Drakeley, Christopher J, Riley, Eleanor M, Kwiatkowski, Dominic P, Rockett, Kirk A, MalariaGEN Consortium, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], London School of Hygiene and Tropical Medicine (LSHTM), National Institute for Biological Standards and Control (NIBSC), Medicines and Healthcare Products Regulatory Agency (MHRA), Nuffield Department of Population Health [Oxford], The Wellcome Trust Sanger Institute [Cambridge], Unité d'Epidémiologie des Maladies Infectieuses, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Immunologie Moléculaire des Parasites, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Malaria Research and Training Center [Bamako, Mali], Université de Bamako, Stockholm University, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), University of Khartoum, KEMRI-Wellcome Trust Research Programme (KWTRP), Tumaini University Makumira, National Institute for Medical Research [Tanzania] (NIMR), University of Edinburgh, University of Colombo [Sri Lanka], MalariaGEN is supported by the Wellcome Trust (077383/Z/05/Z) and by the Foundation for the National Institutes of Health (566) as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative. The Resource Centre for Genomic Epidemiology of Malaria is supported by the Wellcome Trust (090770/Z/09/Z). Support was also provided by the Medical Research Council (G0600718). DPK receives support from the Medical Research Council (G19/9). CCAS was supported by a Wellcome Trust Career Development Fellowship (097364/Z/11/Z). The Wellcome Trust also provides core awards to The Wellcome Trust Centre for Human Genetics (075491/Z/04, 090532/Z/09/Z) and the Wellcome Trust Sanger Institute (077012/Z/05/Z). MTB and BM received funding through the EU Network of Excellence EviMalar. VDM was funded by a Biomalpar (European Community’s Sixth Framework Programme) PhD fellowship. FV was funded by the Italian Malaria Network, sponsored by Compagnia di San Paolo, Turin, Italy. TNW is supported by a Senior Research Fellowship from the Wellcome Trust (091758/Z/10/Z). This study was conducted as part of the Joint Malaria Programme, a collaboration between the National Institute for Medical Research (NIMR), Kilimanjaro Christian Medical College (KCMC), the London School of Hygiene and Tropical Medicine (LSHTM) and the Centre for Medical Parasitology, University of Copenhagen (CMP) with funding from the UK Medical Research Council (GG9901439) and the Danish International Development Agency. CJD is supported by the Wellcome Trust (091924). RD is supported by the University of Colombo Research Grants 2011 (AP/3/2011/PG/15)., European Project: 26843,BIOMALPAR, University of Oxford, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)

Subjects
Male, Hemoglobin, Sickle, Antibodies, Protozoan, Sickle, MESH: Linear Models, MESH: Child, Child, HbAS, MESH: Infant, Newborn, Antibody, CD36, Genotype, Malaria, Sickle cell trait, Adolescent, Adult, Africa South of the Sahara, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Linear Models, Sri Lanka, Young Adult, Infectious Diseases, Parasitology, MESH: Infant, MESH: Young Adult, Protozoan, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Malaria, Antibodies, parasitic diseases, MESH: Antibodies, Protozoan, Hemoglobin, MESH: Africa South of the Sahara, Preschool, MESH: Sri Lanka, MESH: Adolescent, MESH: Humans, Research, MESH: Child, Preschool, MESH: Adult, Newborn, MESH: Hemoglobin, Sickle, MESH: Male, antibody, cd36, genotype, hbas, malaria, sickle cell trait, infectious diseases, parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female
Abstract

Background Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Methods Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Results Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Conclusion Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity. Electronic supplementary material The online version of this article (doi:10.1186/s12936-015-0833-x) contains supplementary material, which is available to authorized users.

Published
2015
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8. Additional file 3: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Abstract

Additional File LFST1A: Details of gene regions selected for genotyping and the SNP assay design details. This file contains a list of the genes from which SNPs were selected and typed for this study. Information is provided on the gene and its genomic location with respect to the Human Reference genome build GRCh37. Also provided is a table containing the assay design details for each SNP used in this study for the Agena Biosciences iPLEX genotyping platform. SNPs are grouped into multiplexes as assigned by the assay design software.

Published
2015
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9. Additional file 17: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Abstract

Additional Figure SF5: Plot for 178 SNPs with logged anti-malarial antibody levels. Plot for the P-values of the analyses of 178 SNPs with logged anti-malarial antibody levels Adjusted for age, gender, parasite density, village (>20), ethnicity (>20), sample month (>20) and study. This is an extension to that shown in the main text and is a reduced dataset as not all sites provided parasitaemia data.

Published
2015
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10. Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer M. G., Corran, Patrick, Risley, Paul, Silva, Nilupa, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Clark, Taane G., Band, Gavin, Clarke, Geraldine M., Spencer, Christopher C. A., Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Ly, Alioune Badara, Mercereau-Puijalon, Odile, Sakuntabhai, Anavaj, Djimde, Abdoulaye, Maiga, Boubacar, Toure, Ousmane, Doumbo, Ogobara K., Dolo, Amagana, Troye-Blomberg, Marita, Mangano, Valentina D., Verra, Frederica, Modiano, David, Bougouma, Edith, Sirima, Sodiomon B., Ibrahim, Muntaser, Hussain, Ayman, Eid, Nahid, Elzein, Abier, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas N., Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Manjurano, Alphaxard, Reyburn, Hugh, Lemnge, Martha, Ishengoma, Deus, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Dewasurendra, Rajika, Drakeley, Christopher J., Riley, Eleanor M., Kwiatkowski, Dominic P., Rockett, Kirk A., Shelton, Jennifer M. G., Corran, Patrick, Risley, Paul, Silva, Nilupa, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Clark, Taane G., Band, Gavin, Clarke, Geraldine M., Spencer, Christopher C. A., Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Ly, Alioune Badara, Mercereau-Puijalon, Odile, Sakuntabhai, Anavaj, Djimde, Abdoulaye, Maiga, Boubacar, Toure, Ousmane, Doumbo, Ogobara K., Dolo, Amagana, Troye-Blomberg, Marita, Mangano, Valentina D., Verra, Frederica, Modiano, David, Bougouma, Edith, Sirima, Sodiomon B., Ibrahim, Muntaser, Hussain, Ayman, Eid, Nahid, Elzein, Abier, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas N., Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Manjurano, Alphaxard, Reyburn, Hugh, Lemnge, Martha, Ishengoma, Deus, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Dewasurendra, Rajika, Drakeley, Christopher J., Riley, Eleanor M., Kwiatkowski, Dominic P., and Rockett, Kirk A.

Abstract

Background: Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Methods: Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP) 4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Results: Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)(4) epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Conclusion: Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demons

Published
2015
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16. Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response.

Author

Hensmann, Meike, Li, Ching, Moss, Catherine, Lindo, Viv, Greer, Fiona, Watts, Colin, Ogun, Solabomi A., Holder, Anthony A., and Langhorne, Jean

Abstract

The 19 kDa C-terminal fragment of the malaria parasite merozoite surface protein 1 (MSP1) is a leading malaria vaccine candidate. In rodents, high antibody levels to this protein confer protective immunity, and can be generated by immunization with the antigen in adjuvants. In natural human infections, however, MSP1-specific antibody responses can be short-lived andcomparatively low, despite repeated exposure to infection. The tightly folded structure of MSP1 is stabilized by five or six disulfide bonds. These bonds impede antigen processing and, thereby, may affect the generation of CD4 T cells providing help for B cells. Asparagine endopeptidase could digest unfolded, but not native MSP1 in vitro. Immunization with unfolded MSP1 resulted in a faster antibody response, and a combination of unfolded and native MSP1 increased antibody responses to the native form. Immunization with either form of the antigen activated similar numbers of CD4 T cells, but, unlike the antibody response, CD4 T cells immunized with one form of MSP1 were able to respond in vitro to the other form of the protein. Although the reduced form of MSP1 does not induce protective antibodies, our data suggest that inclusion of unfolded protein may improve the efficacy of MSP1 as a vaccine. See correction [ABSTRACT FROM AUTHOR]

Published
2004
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17. CD8.

Author

Brookes, Roger H., Pathan, Ansar A., McShane, Helen, Hensmann, Meike, Price, David A., and Hill, Adrian V. S.

Abstract

Animal models of tuberculosis point to a protective role for MHC class I-restricted CD8 T cells, yet it is unclear how these cells protect or whether such findings extend to humans. Here we report that macrophages infected with Mycobacterium tuberculosis, rapidly process and present an early secreted antigenic target (ESAT-6)-specific HLA class I-restricted CD8 T cell epitope. When cocultured with CD8 T cells restricted through classical HLA class I molecules the growth of bacilli within macrophages is significantly impaired after 7 days. Thisslow antimycobacterial activity did not correlate with macrophage lysis but required cell contact. We also found that inhibitors of apoptosis either had no effect or augmented the CD8-mediated suppressive activity, suggesting that an activation signal might be involved. Indeed we show that CD8 T cells were able to activate macrophages through receptors that include CD95 (Fas). Consistent with these findings the CD8-mediated suppression of mycobacterial growth was partially reversed by Fas blockade. These data identify a previously unrecognized CD8 T cell-mediated mechanismused to control an intracellular infection of macrophages. [ABSTRACT FROM AUTHOR]

Published
2003
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19. Additional file 13: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST7Aâ E: Results of site-specific linear regression analysis investigating the effect of age, gender and malaria status as determined by microscopy on antibody levels to the different antibodies measured in the study. This data shows the site-specific analyses of the various epidemiological parameters and antibody measurements.

20. Additional file 16: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST10: Meta-analysis p-values obtained for 178 SNPs passing QC criteria detailed in materials and methods. Details of the analyses for each SNP and antibody across all sites for different genetic inheritance models.

21. Additional file 10: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional figure SF4: Scatter plot of the correlations between residuals from the antibody linear regression models with non-genetic factors at each site and age-group. This plot shows the pairwise correlations (as r2) for each malariaâ malaria antibody pair as a function of each study site. The sites are ordered according to malaria microscopically-positive-prevalence recorded at sample collection (low to high). Several panels are shown according to age-group.

22. Additional file 4: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

MalariaGEN Supplementary Sample Handling Procedures. This file includes more detail on sample handling procedures including extracting DNA, genotyping methodology, ELISA protocols with ELISA data processing.

23. Additional file 9: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional figure SF3: Heatmap matrix plot of the correlations between residuals from the antibody linear regression models with non-genetic factors at each site. Matrix plot of the pairwise correlations as r2 between antibody titres using data from all sites.

24. Additional file 14: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional Table ST8: Results of linear regression analysis investigating the effect of age, gender, malaria status as determined by microscopy and bednet use* on logged antibody levels to AMA1, MSP1, MSP2, NANP and IgE. This table shows the results of the analysis of antibody levels with bednet use. Results shown as betas indicating the direction of effect of the clinical covariates on antibody levels.

25. Additional file 10: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional figure SF4: Scatter plot of the correlations between residuals from the antibody linear regression models with non-genetic factors at each site and age-group. This plot shows the pairwise correlations (as r2) for each malariaâ malaria antibody pair as a function of each study site. The sites are ordered according to malaria microscopically-positive-prevalence recorded at sample collection (low to high). Several panels are shown according to age-group.

26. Additional file 7: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
Statistics::Machine Learning, Statistics::Theory, Statistics::Methodology, Statistics::Computation, 3. Good health
Abstract

Additional Table ST3A-D: Details of the linear regression models used in this study. Model formulae for the various linear regression analyses showing how the different co-variates were used.

27. Additional file 6: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
body regions, nervous system, sense organs, equipment and supplies, 3. Good health
Abstract

Additional Figure SF2: Histograms of residuals from antibody linear regression models with non-genetic factors. Histograms of the residuals from the antibody linear regression model analysis with non-genetic factors.

28. Additional file 13: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST7Aâ E: Results of site-specific linear regression analysis investigating the effect of age, gender and malaria status as determined by microscopy on antibody levels to the different antibodies measured in the study. This data shows the site-specific analyses of the various epidemiological parameters and antibody measurements.

29. Additional file 2: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST2: Details of covariates adjusted for in linear regression analysis of non-genetic factors with logged antibody levels, their relevance to the study and their previous association(s) with malaria or anti-malarial antibodies. Information on the covariates used in this study as con-variates in the various analyses.

30. Additional file 5: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
body regions, endocrine system, nervous system, sense organs, equipment and supplies, 3. Good health
Abstract

Additional Figure SF1: Histograms of logged antibody levels before further manipulations were made. Histograms of the logged antibody titres across all samples for each antibody measured in this study.

31. Additional file 15: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST9: Details of 196 genotyped SNPs and their derived allele frequencies at each site. This table shows allele frequencies for each SNP analysed in this study according to each study site.

32. Additional file 16: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST10: Meta-analysis p-values obtained for 178 SNPs passing QC criteria detailed in materials and methods. Details of the analyses for each SNP and antibody across all sites for different genetic inheritance models.

33. Additional file 11: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional table ST5: Linear regression analysis of the correlations between residuals from the malaria antibody pairs. This data shows the results of the analysis of the correlations between antibodies.

34. Additional file 8: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional Table ST4: Results of linear regression analysis investigating the effect of age, gender and HbS genotype on parasite density in malaria-positive individuals using combined site data. Results of linear regression analysis investigating the effect of age, gender and HbS genotype on parasite density in malaria-positive individuals using combined data. This is an extension to that shown in the main text and is a reduced dataset as not all sites provided parasitaemia data.

35. Additional file 15: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST9: Details of 196 genotyped SNPs and their derived allele frequencies at each site. This table shows allele frequencies for each SNP analysed in this study according to each study site.

36. Additional file 6: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
body regions, nervous system, sense organs, equipment and supplies, 3. Good health
Abstract

Additional Figure SF2: Histograms of residuals from antibody linear regression models with non-genetic factors. Histograms of the residuals from the antibody linear regression model analysis with non-genetic factors.

37. Additional file 4: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

MalariaGEN Supplementary Sample Handling Procedures. This file includes more detail on sample handling procedures including extracting DNA, genotyping methodology, ELISA protocols with ELISA data processing.

38. Additional file 18: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional Figure SF6: Forest plot of the association of A: CD36 (rs3211938), B: LOC441108 (rs2522051), C: RTN3 (rs542998) and D: P4HA2 (rs156029) with antibody levels to AMA1, MSP1, MSP2 and NANP. Forest plots of the betas obtained from meta-analysis of results obtained from linear regression models of SNP with logged antibody levels, adjusted for relevant clinical covariates.

39. Additional file 11: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional table ST5: Linear regression analysis of the correlations between residuals from the malaria antibody pairs. This data shows the results of the analysis of the correlations between antibodies.

40. Additional file 7: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
Statistics::Machine Learning, Statistics::Theory, Statistics::Methodology, Statistics::Computation, 3. Good health
Abstract

Additional Table ST3A-D: Details of the linear regression models used in this study. Model formulae for the various linear regression analyses showing how the different co-variates were used.

41. Additional file 1: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
education, 3. Good health
Abstract

Additional Table ST1 Details of Principal Investigators and Ethics Review Committees for each site. Details of Principal Investigators and Ethics Review Committees for each site.

42. Additional file 9: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional figure SF3: Heatmap matrix plot of the correlations between residuals from the antibody linear regression models with non-genetic factors at each site. Matrix plot of the pairwise correlations as r2 between antibody titres using data from all sites.

43. Additional file 14: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
parasitic diseases, 3. Good health
Abstract

Additional Table ST8: Results of linear regression analysis investigating the effect of age, gender, malaria status as determined by microscopy and bednet use* on logged antibody levels to AMA1, MSP1, MSP2, NANP and IgE. This table shows the results of the analysis of antibody levels with bednet use. Results shown as betas indicating the direction of effect of the clinical covariates on antibody levels.

44. Additional file 5: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
body regions, endocrine system, nervous system, sense organs, equipment and supplies, 3. Good health
Abstract

Additional Figure SF1: Histograms of logged antibody levels before further manipulations were made. Histograms of the logged antibody titres across all samples for each antibody measured in this study.

45. Additional file 2: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
3. Good health
Abstract

Additional Table ST2: Details of covariates adjusted for in linear regression analysis of non-genetic factors with logged antibody levels, their relevance to the study and their previous association(s) with malaria or anti-malarial antibodies. Information on the covariates used in this study as con-variates in the various analyses.

46. Additional file 1: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Author

Shelton, Jennifer, Corran, Patrick, Risley, Paul, Nilupa Silva, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Taane Clark, Band, Gavin, Clarke, Geraldine, Spencer, Christopher, Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama, Alioune Ly, Mercereau-Puijalon, Odile, Anavaj Sakuntabhai, Abdoulaye DjimdĂŠ, Boubacar Maiga, Ousmane TourĂŠ, Ogobara Doumbo, Amagana Dolo, Troye-Blomberg, Marita, Mangano, Valentina, Verra, Frederica, Modiano, David, Bougouma, Edith, Sodiomon Sirima, Muntaser Ibrahim, Hussain, Ayman, Eid, Nahid, Abier Elzein, Mohammed, Hiba, Elhassan, Ahmed, Elhassan, Ibrahim, Williams, Thomas, Ndila, Carolyne, Macharia, Alexander, Marsh, Kevin, Alphaxard Manjurano, Reyburn, Hugh, Lemnge, Martha, Deus Ishengoma, Carter, Richard, Karunaweera, Nadira, Fernando, Deepika, Rajika Dewasurendra, Drakeley, Christopher, Riley, Eleanor, Kwiatkowski, Dominic, and Rockett, Kirk

Subjects
education, 3. Good health
Abstract

Additional Table ST1 Details of Principal Investigators and Ethics Review Committees for each site. Details of Principal Investigators and Ethics Review Committees for each site.

47. CD8+ T cell-mediated suppression of intracellular Mycobacterium tuberculosis growth in activated human macrophages.

Author

Brookes RH, Pathan AA, McShane H, Hensmann M, Price DA, and Hill AV

Subjects
Cell Communication, Cell Line, Humans, fas Receptor physiology, Macrophage Activation, Macrophages microbiology, Mycobacterium tuberculosis growth & development, T-Lymphocytes, Cytotoxic immunology
Abstract

Animal models of tuberculosis point to a protective role for MHC class I-restricted CD8(+) T cells, yet it is unclear how these cells protect or whether such findings extend to humans. Here we report that macrophages infected with Mycobacterium tuberculosis, rapidly process and present an early secreted antigenic target (ESAT-6)-specific HLA class I-restricted CD8(+) T cell epitope. When cocultured with CD8(+) T cells restricted through classical HLA class I molecules the growth of bacilli within macrophages is significantly impaired after 7 days. This slow antimycobacterial activity did not correlate with macrophage lysis but required cell contact. We also found that inhibitors of apoptosis either had no effect or augmented the CD8-mediated suppressive activity, suggesting that an activation signal might be involved. Indeed we show that CD8(+) T cells were able to activate macrophages through receptors that include CD95 (Fas). Consistent with these findings the CD8-mediated suppression of mycobacterial growth was partially reversed by Fas blockade. These data identify a previously unrecognized CD8(+) T cell-mediated mechanism used to control an intracellular infection of macrophages.

Published
2003
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