Evidence map›Paper›PMID 33637093›Full record

ArticleMalaria journal2021

Optimization of whole-genome sequencing of Plasmodium falciparum from low-density dried blood spot samples.

Noam B Teyssier, Anna Chen, Elias M Duarte, Rene Sit, Bryan Greenhouse, Sofonias K Tessema

Abstract read
In one paragraph

Article in Malaria journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed.

  1. Trial
  2. Article
  3. Challenges in Malaria Diagnosis and Treatment in Kinshasa Province, Democratic Republic of the Congo.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Malaria control and the unexpected spread of diagnostic-resistantbioRxiv : the preprint server for biology · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Artemisinin resistantmedRxiv : the preprint server for health sciences · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Noam B TeyssierDepartment of Medicine, EPPIcenter, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-4001-6296
Anna ChenDepartment of Medicine, EPPIcenter, University of California, San Francisco, CA, USA.
Elias M DuarteDepartment of Medicine, EPPIcenter, University of California, San Francisco, CA, USA.
Rene SitChan Zuckerberg Biohub, San Francisco, CA, USA.
Bryan GreenhouseDepartment of Medicine, EPPIcenter, University of California, San Francisco, CA, USA. sofoniask.tessema@ucsf.edu.
Sofonias K TessemaDepartment of Medicine, EPPIcenter, University of California, San Francisco, CA, USA. sofoniask.tessema@ucsf.edu.

Funding

Mentoring translational scientists in international infectious disease researchK24AI144048 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Bryan R Greenhouse · 2019 to 2026
$1.6M
Bill & Melinda Gates Foundation OPP1132226NIAID NIH HHS K24 AI144048
6 · The paper itself

Abstract

backgroundWhole-genome sequencing (WGS) is becoming increasingly useful to study the biology, epidemiology, and ecology of malaria parasites. Despite ease of sampling, DNA extracted from dried blood spots (DBS) has a high ratio of human DNA compared to parasite DNA, which poses a challenge for downstream genetic analyses. The effects of multiple methods for DNA extraction, digestion of methylated DNA, and amplification were evaluated on the quality and fidelity of WGS data recovered from DBS.

methodsLow parasite density mock DBS samples were created, extracted either with Tween-Chelex or QIAamp, treated with or without McrBC, and amplified with one of three different amplification techniques (two sWGA primer sets and one rWGA). Extraction conditions were evaluated on performance of sequencing depth, percentiles of coverage, and expected SNP concordance.

resultsAt 100 parasites/μL, Chelex-Tween-McrBC samples had higher coverage (5 × depth = 93% genome) than QIAamp extracted samples (5 × depth = 76% genome). The two evaluated sWGA primer sets showed minor differences in overall genome coverage and SNP concordance, with a newly proposed combination of 20 primers showing a modest improvement in coverage over those previously published.

conclusionsOverall, Tween-Chelex extracted samples that were treated with McrBC digestion and are amplified using 6A10AD sWGA conditions had minimal dropout rate, higher percentages of coverage at higher depth, and more accurate SNP concordance than QiaAMP extracted samples. These findings extend the results of previously reported methods, making whole genome sequencing accessible to a larger number of low density samples that are commonly encountered in cross-sectional surveys.

Indexed as

Dried Blood Spot TestingHumansPlasmodium falciparumWhole Genome SequencingDried blood spotsMalariaMcrBCP. falciparumSelective whole genome amplificationTween-ChelexWhole genome sequencing

Identifiers

PMID33637093
PMCPMC7912882

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.