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Article ; Online: An optimized GATK4 pipeline for Plasmodium falciparum whole genome sequencing variant calling and analysis

Karamoko Niaré / Bryan Greenhouse / Jeffrey A. Bailey

Malaria Journal, Vol 22, Iss 1, Pp 1-

2023 Volume 11

Abstract: Abstract Background Accurate variant calls from whole genome sequencing (WGS) of Plasmodium falciparum infections are crucial in malaria population genomics. Here a falciparum variant calling pipeline based on GATK version 4 (GATK4) was optimized and ... ...

Abstract	Abstract Background Accurate variant calls from whole genome sequencing (WGS) of Plasmodium falciparum infections are crucial in malaria population genomics. Here a falciparum variant calling pipeline based on GATK version 4 (GATK4) was optimized and applied to 6626 public Illumina WGS samples. Methods Control WGS and accurate PacBio assemblies of 10 laboratory strains were leveraged to optimize parameters that control the heterozygosity, local assembly region size, ploidy, mapping and base quality in both GATK HaplotypeCaller and GenotypeGVCFs. From these controls, a high-quality training dataset was generated to recalibrate the raw variant data. Results On current high-quality samples (read length = 250 bp, insert size = 405–524 bp), the optimized pipeline shows improved sensitivity (86.6 ± 1.7% for SNPs and 82.2 ± 5.9% for indels) compared to the default GATK4 pipeline (77.7 ± 1.3% for SNPs; and 73.1 ± 5.1% for indels, adjusted P < 0.001) and previous variant calling with GATK version 3 (GATK3, 70.3 ± 3.0% for SNPs and 59.7 ± 5.8% for indels, adjusted P < 0.001). Its sensitivity on simulated mixed infection samples (80.8 ± 6.1% for SNPs and 78.3 ± 5.1% for indels) was again improved relative to default GATK4 (68.8 ± 6.0% for SNPs and 38.9 ± 0.7% for indels, adjusted, adjusted P < 0.001). Precision was high and comparable across all pipelines on each type of data tested. The resulting combination of high-quality SNPs and indels increases the resolution of local population population structure detection in sub-Saharan Africa. Finally, increasing ploidy improves the detection of drug resistance mutations and estimation of complexity of infection. Conclusions Overall, this study provides an optimized falciparum GATK4 pipeline resource for variant calling which should help improve genomic studies of malaria.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: coiaf

Aris Paschalidis / Oliver J Watson / Ozkan Aydemir / Robert Verity / Jeffrey A Bailey

PLoS Computational Biology, Vol 19, Iss 6, p e

Directly estimating complexity of infection with allele frequencies.

2023 Volume 1010247

Abstract: In malaria, individuals are often infected with different parasite strains. The complexity of infection (COI) is defined as the number of genetically distinct parasite strains in an individual. Changes in the mean COI in a population have been shown to ... ...

Abstract	In malaria, individuals are often infected with different parasite strains. The complexity of infection (COI) is defined as the number of genetically distinct parasite strains in an individual. Changes in the mean COI in a population have been shown to be informative of changes in transmission intensity with a number of probabilistic likelihood and Bayesian models now developed to estimate the COI. However, rapid, direct measures based on heterozygosity or FwS do not properly represent the COI. In this work, we present two new methods that use easily calculated measures to directly estimate the COI from allele frequency data. Using a simulation framework, we show that our methods are computationally efficient and comparably accurate to current approaches in the literature. Through a sensitivity analysis, we characterize how the distribution of parasite densities, the assumed sequencing depth, and the number of sampled loci impact the bias and accuracy of our two methods. Using our developed methods, we further estimate the COI globally from Plasmodium falciparum sequencing data and compare the results against the literature. We show significant differences in the estimated COI globally between continents and a weak relationship between malaria prevalence and COI.
Keywords	Biology (General) ; QH301-705.5
Subject code	310
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Replicative fitness and pathogenicity of primate lentiviruses in lymphoid tissue, primary human and chimpanzee cells

Denis M. Tebit / Gabrielle Nickel / Richard Gibson / Myriam Rodriguez / Nicolas J. Hathaway / Katie Bain / Angel L. Reyes-Rodriguez / Pascal Ondoa / Jonathan L. Heeney / Yue Li / Jennifer Bongorno / David Canaday / David McDonald / Jeffrey A. Bailey / Eric J. Arts

EBioMedicine, Vol 100, Iss , Pp 104965- (2024)

relation to possible jumps to humansResearch in context

2024

Abstract: Summary: Background: Simian immunodeficiency viruses (SIV) have been jumping between non-human primates in West/Central Africa for thousands of years and yet, the HIV-1 epidemic only originated from a primate lentivirus over 100 years ago. Methods: This ... ...

Abstract	Summary: Background: Simian immunodeficiency viruses (SIV) have been jumping between non-human primates in West/Central Africa for thousands of years and yet, the HIV-1 epidemic only originated from a primate lentivirus over 100 years ago. Methods: This study examined the replicative fitness, transmission, restriction, and cytopathogenicity of 22 primate lentiviruses in primary human lymphoid tissue and both primary human and chimpanzee peripheral blood mononuclear cells. Findings: Pairwise competitions revealed that SIV from chimpanzees (cpz) had the highest replicative fitness in human or chimpanzee peripheral blood mononuclear cells, even higher fitness than HIV-1 group M strains responsible for worldwide epidemic. The SIV strains belonging to the “HIV-2 lineage” (including SIVsmm, SIVmac, SIVagm) had the lowest replicative fitness. SIVcpz strains were less inhibited by human restriction factors than the “HIV-2 lineage” strains. SIVcpz efficiently replicated in human tonsillar tissue but did not deplete CD4+ T-cells, consistent with the slow or nonpathogenic disease observed in most chimpanzees. In contrast, HIV-1 isolates and SIV of the HIV-2 lineage were pathogenic to the human tonsillar tissue, almost independent of the level of virus replication. Interpretation: Of all primate lentiviruses, SIV from chimpanzees appears most capable of infecting and replicating in humans, establishing HIV-1. SIV from other Old World monkeys, e.g. the progenitor of HIV-2, replicate slowly in humans due in part to restriction factors. Nonetheless, many of these SIV strains were more pathogenic than SIVcpz. Either SIVcpz evolved into a more pathogenic virus while in humans or a rare SIVcpz, possibly extinct in chimpanzees, was pathogenic immediately following the jump into human. Funding: Support for this study to E.J.A. was provided by the NIH/NIAID R01 AI49170 and CIHR project grant 385787. Infrastructure support was provided by the NIH CFAR AI36219 and Canadian CFI/Ontario ORF 36287. Efforts of J.A.B. and N.J.H. was ...
Keywords	HIV-1 ; Zoonosis ; Primate lentiviruses ; Pathogenesis ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	571
Language	English
Publishing date	2024-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Distinctive Kaposi Sarcoma-Associated Herpesvirus Serological Profile during Acute Plasmodium falciparum Malaria Episodes

Peter O. Oluoch / Catherine S. Forconi / Cliff I. Oduor / Dominic A. Ritacco / Hoseah M. Akala / Jeffrey A. Bailey / Jonathan J. Juliano / John M. Ong’echa / Christian Münz / Ann M. Moormann

International Journal of Molecular Sciences, Vol 24, Iss 6711, p

2023 Volume 6711

Abstract: The seroprevalence of Kaposi sarcoma-associated herpesvirus (KSHV) and the incidence of endemic Kaposi sarcoma (KS) overlap with regions of malaria endemicity in sub-Saharan Africa. Multiple studies have shown an increased risk of KSHV seroconversion in ... ...

Abstract	The seroprevalence of Kaposi sarcoma-associated herpesvirus (KSHV) and the incidence of endemic Kaposi sarcoma (KS) overlap with regions of malaria endemicity in sub-Saharan Africa. Multiple studies have shown an increased risk of KSHV seroconversion in children from high malaria compared to low malaria regions; however, the impact of acute episodes of Plasmodium falciparum ( P. falciparum ) malaria on KSHV’s biphasic life cycle and lytic reactivation has not been determined. Here, we examined KSHV serological profiles and viral loads in 134 children with acute malaria and 221 healthy children from high malaria regions in Kisumu, as well as 77 healthy children from low malaria regions in Nandi. We assayed KSHV, Epstein–Barr virus (EBV), and P. falciparum malaria antibody responses in these three by multiplexed Luminex assay. We confirmed that KSHV seroprevalence was significantly associated with malaria endemicity (OR = 1.95, 1.18–3.24 95% CI, p = 0.01) with 71–77% seropositivity in high-malaria (Kisumu) compared to 28% in low-malaria (Nandi) regions. Furthermore, KSHV serological profiles during acute malaria episodes were distinct from age-matched non-malaria-infected children from the same region. Paired IgG levels also varied after malaria treatment, with significantly higher anti-ORF59 at day 0 but elevated ORF38, ORF73, and K8.1 at day 3. Acute malaria episodes is characterized by perturbation of KSHV latency in seropositive children, providing further evidence that malaria endemicity contributes to the observed increase in endemic KS incidence in sub-Saharan Africa.
Keywords	Kaposi sarcoma-associated herpesvirus ; Epstein–Barr virus ; acute malaria infection ; endemic Kaposi sarcoma ; sub-Saharan Africa ; lytic replication ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Immediate pools of malaria infections at diagnosis combined with targeted deep sequencing accurately quantifies frequency of drug resistance mutations

Ozkan Aydemir / Benedicta Mensah / Patrick W. Marsh / Benjamin Abuaku / James Leslie Myers-Hansen / Jeffrey A. Bailey / Anita Ghansah

PeerJ, Vol 9, p e

2021 Volume 11794

Abstract: Antimalarial resistance surveillance in sub-Saharan Africa is often constrained by logistical and financial challenges limiting its breadth and frequency. At two sites in Ghana, we have piloted a streamlined sample pooling process created immediately by ... ...

Abstract	Antimalarial resistance surveillance in sub-Saharan Africa is often constrained by logistical and financial challenges limiting its breadth and frequency. At two sites in Ghana, we have piloted a streamlined sample pooling process created immediately by sequential addition of positive malaria cases at the time of diagnostic testing. This streamlined process involving a single tube minimized clinical and laboratory work and provided accurate frequencies of all known drug resistance mutations after high-throughput targeted sequencing using molecular inversion probes. Our study validates this method as a cost-efficient, accurate and highly-scalable approach for drug resistance mutation monitoring that can potentially be applied to other infectious diseases such as tuberculosis.
Keywords	Malaria ; Plasmodium falciparum ; Drug resistance ; Molecular inversion probes ; Molecular surveillance ; Medicine ; R ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia

Mercedeh Movassagh / Cliff Oduor / Catherine Forconi / Ann M. Moormann / Jeffrey A. Bailey

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 10

Abstract: Abstract Epstein Barr virus (EBV) is the etiologic agent involved in numerous human cancers. After infecting the host, EBV establishes a latent infection, with low levels of messenger RNA (mRNA) and protein expression, evolved to evade immune recognition. ...

Abstract	Abstract Epstein Barr virus (EBV) is the etiologic agent involved in numerous human cancers. After infecting the host, EBV establishes a latent infection, with low levels of messenger RNA (mRNA) and protein expression, evolved to evade immune recognition. Conversely, EBV microRNAs (miRNA) are expressed ubiquitously and abundantly within infected cells. Their role in tumor biology and clinical outcomes across the spectrum of cancer is not fully explained. Here, we applied our bioinformatics pipeline for quantitative EBV miRNA detection to examine sequencing data of 8,955 individual tumor samples across 27 tumor types representing the breadth of cancer. We uncover an association of intermediate levels of viral miRNA with decreased survival in adult acute myeloid leukemia (AML) patients (P = 0.00013). Prognostic modeling of this association suggests that increased EBV miRNA levels represent an independent risk factor for poor patient outcomes. Furthermore, we explore differences in expression between elevated and absent viral miRNA loads in adult AML tumors finding that EBV positivity was associated with proinflammatory signals. Together, given no associations were found for pediatric AML, our analyses suggests EBV positivity has the potential for being a prognostic biomarker and might represent a surrogate measure related to immune impairment in adult patients.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2019-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The prevalence of molecular markers of resistance to sulfadoxine-pyrimethamine among pregnant women at first antenatal clinic attendance and delivery in the forest-savannah area of Ghana.

David Kwame Dosoo / Jeffrey A Bailey / Kwaku Poku Asante / Felix Boakye Oppong / Karamoko Niaré / Jones Opoku-Mensah / Seth Owusu-Agyei / Brian Greenwood / Daniel Chandramohan

PLoS ONE, Vol 17, Iss 8, p e

2022 Volume 0271489

Abstract: Intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is used to prevent malaria and associated unfavorable maternal and foetal outcomes in pregnancy in moderate to high malaria transmission areas. Effectiveness of ... ...

Abstract	Intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is used to prevent malaria and associated unfavorable maternal and foetal outcomes in pregnancy in moderate to high malaria transmission areas. Effectiveness of IPTp-SP is, however, threatened by mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes which confer resistance to pyrimethamine and sulfadoxine, respectively. This study determined the prevalence of molecular markers of SP resistance among pregnant women in a high malaria transmission area in the forest-savannah area of Ghana. Genomic DNA was extracted from 286 P. falciparum-positive dried blood spots obtained from pregnant women aged ≥18 years (255 at first Antenatal Care (ANC) clinic visit and 31 at delivery from 2017 to 2019) using Chelex 100. Mutations in Pfdhfr and Pfdhps genes were detected using molecular inversion probes and next generation sequencing. In the Pfdhfr gene, single nucleotide polymorphisms (SNPs) were detected in 83.1% (157/189), 92.0% (173/188) and 91.0% (171/188) at codons 51, 59, and 108 respectively in samples collected at first ANC visit, while SNPs were detected in 96.6 (28/29), 96.6% (28/29) and 96.8% (30/31) in isolates collected at delivery. The Pfdhfr triple mutant N51I, C59R and S108N (IRN) was carried by 80.5% (128/159) and 96.5% (28/29) of the typed isolates collected at ANC visit and at delivery respectively. In the Pfdhps gene, SNPs were detected in 0.6% (1/174), 76.2% (138/181), 33.2% (60/181), 1.2% (2/174), 0% (0/183), and 16.6% (27/173) at codons 431, 436, 437, 540, 581 and 613 respectively in samples collected at ANC, and 0% (0/25), 72% (18/25), 40% (10/25), 3.6% (1/25), 0% (0/29) and 7.4% (2/27) in samples collected at delivery. Quadruple mutant Pfdhfr N51I, C59R, and S108N + Pfdhps A437G (IRN-GK) was present in 25.8% (33/128) and 34.8% (8/23) of isolates at ANC and at delivery respectively. Quintuple mutant alleles Pfdhfr N51I, C59R, and S108N + Pfdhps A437G ...
Keywords	Medicine ; R ; Science ; Q
Subject code	580
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Decreased susceptibility of Plasmodium falciparum to both dihydroartemisinin and lumefantrine in northern Uganda

Patrick K. Tumwebaze / Melissa D. Conrad / Martin Okitwi / Stephen Orena / Oswald Byaruhanga / Thomas Katairo / Jennifer Legac / Shreeya Garg / David Giesbrecht / Sawyer R. Smith / Frida G. Ceja / Samuel L. Nsobya / Jeffrey A. Bailey / Roland A. Cooper / Philip J. Rosenthal

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 12

Abstract: In this work, susceptibilities to two key antimalarials, dihydroartemisinin and lumefantrine, were associated with multiple genetic polymorphisms in Plasmodium falciparum, and were lower in northern Uganda, where resistance-mediating mutations have ... ...

Abstract	In this work, susceptibilities to two key antimalarials, dihydroartemisinin and lumefantrine, were associated with multiple genetic polymorphisms in Plasmodium falciparum, and were lower in northern Uganda, where resistance-mediating mutations have emerged, compared to eastern Uganda.
Keywords	Science ; Q
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell lines

Elliott D SoRelle / Joanne Dai / Emmanuela N Bonglack / Emma M Heckenberg / Jeffrey Y Zhou / Stephanie N Giamberardino / Jeffrey A Bailey / Simon G Gregory / Cliburn Chan / Micah A Luftig

eLife, Vol

2021 Volume 10

Abstract: Lymphoblastoid cell lines (LCLs) are generated by transforming primary B cells with Epstein–Barr virus (EBV) and are used extensively as model systems in viral oncology, immunology, and human genetics research. In this study, we characterized single-cell ...

Abstract	Lymphoblastoid cell lines (LCLs) are generated by transforming primary B cells with Epstein–Barr virus (EBV) and are used extensively as model systems in viral oncology, immunology, and human genetics research. In this study, we characterized single-cell transcriptomic profiles of five LCLs and present a simple discrete-time simulation to explore the influence of stochasticity on LCL clonal evolution. Single-cell RNA sequencing (scRNA-seq) revealed substantial phenotypic heterogeneity within and across LCLs with respect to immunoglobulin isotype; virus-modulated host pathways involved in survival, activation, and differentiation; viral replication state; and oxidative stress. This heterogeneity is likely attributable to intrinsic variance in primary B cells and host–pathogen dynamics. Stochastic simulations demonstrate that initial primary cell heterogeneity, random sampling, time in culture, and even mild differences in phenotype-specific fitness can contribute substantially to dynamic diversity in populations of nominally clonal cells.
Keywords	Epstein-Barr virus ; lymphoblastoid cell lines ; virus infection ; NFkappaB ; B-cell differentiation ; systems modeling ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correction

Elliott D SoRelle / Joanne Dai / Emmanuela N Bonglack / Emma M Heckenberg / Jeffrey Y Zhou / Stephanie N Giamberardino / Jeffrey A Bailey / Simon G Gregory / Cliburn Chan / Micah A Luftig

eLife, Vol

Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell lines

2021 Volume 10

Keywords	Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
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Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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