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Project Notes for Research Internship in the Lab of Aurelien Tellier

Overview

Population Structure: admixture/structure and dapc analysis
Diversity stats: Diversity and Tajima’s D and estimation of recombination events. \ SFS: Calaculation of the unfolded sfs by polarizing some snp with P. reichenowi outgroup. \

Final report can be found in ./report/report.pdf!

Data

vcf files downloaded from: “ftp://ngs.sanger.ac.uk/production/malaria/Resource/34/Pf7_vcf/”

SNP filtering with bcf tools.

Filtering for Quality control pass (?), bialleic snps…

bcftools view \
    --include 'FILTER="PASS" && N_ALT=1 && TYPE="snp"'\
    --samples-file $samples_dir/Pf7_african_samples_ids.txt \
    --output-type z\
    --output-file  Pf3D7_02_v3.SNP.vcf \
    Pf3D7_02_v3.pf7.vcf.gz

bcftools index -t Pf3D7_02_v3.SNP.vcf

The average VQSLOD value for the 1846 african samples, filtered only by the above is 4.215 and 4.238 for chr11 and chr2, respectively.

Unfiltered (all quality)

chr2chr11
SNPs83,810231,511
avg. VQSLOD4.2384.215

Filtered (VQSLOD > 5.0)

chr2chr11
SNPs16,26944,040
avg. VQSLOD7.4817.427

Set the ‘heterozygote’ GTs to ./.

bcftools filter -S . -e 'GT=="het"' chr2/Pf3D7_02_v3.afr_samples.qSNP.vcf.gz -o chr2/Pf3D7_02_v3.afr_samples.qSNP.GT_filtered.vcf -Oz

Query snp count data for the sfs

bcftools query -f '%POS %REF %ALT %AF %AC %AN\n' Pf3D7_02_v3.afr_samples.qSNP.GT_filtered.vcf.gz > Pf7.02.vcf.qSNP.AF_AC_AN.txt

P.vivax data?

https://wellcomeopenresearch.org/articles/7-136/v1

Pf7 populations

Kenya

https://www.malariagen.net/apps/pf7/countries/KE

  • 285 samples from the Year = 2010-2014 & QC.pass = “True” at the locations Kilifi and Kisumu.

Upper River Gambia

https://www.malariagen.net/apps/pf7/countries/GM

  • 452 samples from Upper River and the years 2013-2017

Democratic Republic of Congo

  • 520 samples, 2012-2016, QC.pass = True

Tanzania

  • 589 samples (2010-2014), QC.pass = True

Other candidates

  • Myanmar, Kayin (631 samples, 2016-2017)
  • Malawi, Chikawa (231 samples, 2011)

Vivax data set from similar locations?

Unfolded sfs

Genome alignment

MUmer version 4 to align the outgroup PrCDCD to ref Pf3D7. Use R script to visualize alignment success: https://taylorreiter.github.io/2019-05-11-Visualizing-NUCmer-Output/

Pf7-PrCDC

Nucleotide substitutions between Pf7 reference and PrCDC assemebled sequence: 25353

Overlapping with the snps from the vcf file: 927

P.reichenowi as an outgroup

The first P. reichenowi reference genome PrCDC was assembled by mapping to Pf7 reference genome (cite:&otto-2014-genom-sequen) Reference genome PrSY57 has been constructed by mapping to PrCDC (cite:&sundararaman-2016-genom-crypt).

Check the divergence between PrSY57 and Pf7. If there is too much intra-specific polymorphism, we cannot determine the ancestral state of the sample polymorphisms. How to do this? Alignment or mapping?

How to set the anchestral allele information in the outgroup

PCA and DAPC

https://grunwaldlab.github.io/Population_Genetics_in_R/DAPC.html

use dapc tutorial to run dapc with k-1 retained components to avaoid overfitting the data.

Questions

  • What does plasmodiums parasitic lifestyle traits contribute it’s transmission demography (ie. fluctuating population sizes or mulitple merger events) and adative processes (such as positive selection and/or coevolution)?
  • Do we find signatures of multiple mergers or dormancy in P. falciparum populations?
  • Maybe: What signatures do the Pfsa loci show, when accounting for their demography? What about compared to genes under positive selection?

Reading list

Citations and PDF files can be found in the ~/biblio directory.

Plasmodium Genomics

  • Rich et al., 2000: Population structure and recent evolution of Plasmodium falciparum; cite:&rich-2000-popul-struc;
  • Nderu et al., 2019: Genetic diversity and population structure of P. falciparum in Kenyan-Ugandan border areas; cite:&nderu-2019-genet-diver;
  • Amambua-Ngwa et al., 2019: Major subpopulations of P. falciparum in sub-Saharan Africa; cite:&amambua-ngwa-2019-major-subpop;
  • Meyer et al., 2002: Genetic diversity of P. falciparum: asexual stages; cite:&meyer-2002-review;
  • Benavente, 2021: Genetic structure and selection patterns of Plasmodium vivax in South Asia and East Afrika; cite:&benavente-2021-distin-genet;
  • Nygaard et al, 2010: Long- and Short-term selective forces on Malaria Parasite Genomes;cite:&nygaard-2010-long-short
  • Sundararaman et al. 2016: Genomes of cryptic chimpanzee Plasmodium reveal key evolutionary events leading to human malaria;cite:&sundararaman-2016-genom-crypt
  • Otto et al, 2014: Genome sequencing of chimpanzee malaria parasite reveals possible pathways of adaptation to human hosts; cite:&otto-2014-genom-sequen
  • Pearson et al., 2016: Genomic analysis of local variation and recent evolution in Plasmodium vivax; cite:&nygaard-2010-long-short
  • Naung et al., 2022: Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens;cite:&naung-2022-global-diver
  • Noviyanti et al., 2015: Contrasting transmission dynamics of co-endemic Plasmodium;cite:&noviyanti-2015-contr-trans

Human-parasite interactions

  • Band, 2021: Malaria Protection due to Sickle Haemoglobin Depends on Parasite Genotype; cite:&band-2021-malar-protec;
  • Raberg, 2023: Human and Pathogen Genotype-By-Genotype Interactions in the Light of Coevolution theory; cite:&raberg-2023-human-pathog;

Coevolution Theory

  • Brown and Tellier, 2011: Plant-parasite coevolution: Bridging the Gap between Genetics and Ecology; cite:&brown-2011-plant-paras-coevol;
  • Tellier and Brown, 2021: Theory of Host-Parasite Coevolution: From Ecology to Genomics; cite:&tellier-2021-theor-host;
  • Maerkle, 2021: Genomic approaches to study antagonistic coevolution in host and parasites; cite:&maerkle-2021-novel-genom;

Links

Pf7 Data Viewer

https://www.malariagen.net/apps/pf7/

P.reichenowi ftp

ftp://ftp.sanger.ac.uk/pub/project/pathogens/Plasmodium/reichenowi/

Kevin Korfmann Kenya Workshop GitHub

https://kevinkorfmann.github.io/workshop-kenya/session_1.html

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