Evidence map›Paper›PMID 22038251›Full record

ArticleGenome research2011

Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance.

Tim Downing, Hideo Imamura, Saskia Decuypere, Taane G Clark, Graham H Coombs, James A Cotton, James D Hilley, Simonne de Doncker, Ilse Maes, Jeremy C Mottram and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 258 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
258citing papers in PubMed, 1 pooled it
–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

258 citing papers in PubMed, 1 synthesis or guideline pooled it, 430 citations in OpenAlex.

  1. Pooled it
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  5. Article
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  7. Article
  8. Article
  9. Review
  10. CRISPR-Cas13b mediated gene knockdowns in Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2025
    Article
  11. Article
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  15. Unraveling the Genome Diversity ofLife (Basel, Switzerland) · 2025
    Review
  16. Article
  17. Article
  18. Article
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  20. Article

198 more citing papers are in PubMed but not listed here.

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

20 authors at 8 institutions in 5 countries.

Tim DowningWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, United Kingdom.
Hideo Imamura
Saskia Decuypere
Taane G Clark
Graham H Coombs
James A Cotton
James D Hilley
Simonne de Doncker
Ilse Maes
Jeremy C Mottram
Mike A Quail
Suman Rijal
Mandy Sanders
Gabriele Schönian
Olivia Stark
Shyam Sundar
Manu Vanaerschot
Christiane Hertz-Fowler
Jean-Claude Dujardin
Matthew Berriman
Instituut voor Tropische Geneeskunde · BEWellcome Sanger Institute · GBInstitut für Hygiene und Umwelt · DEWellcome Centre for Molecular Parasitology · GBB.P. Koirala Institute of Health Sciences · NPInstitute of Medical Sciences · INUniversity of London · GBUniversity of Strathclyde · GB

Funding

Wellcome TrustWellcome Trust 076355Wellcome Trust 085775/Z/08/Z
6 · The paper itself

Abstract

Visceral leishmaniasis is a potentially fatal disease endemic to large parts of Asia and Africa, primarily caused by the protozoan parasite Leishmania donovani. Here, we report a high-quality reference genome sequence for a strain of L. donovani from Nepal, and use this sequence to study variation in a set of 16 related clinical lines, isolated from visceral leishmaniasis patients from the same region, which also differ in their response to in vitro drug susceptibility. We show that whole-genome sequence data reveals genetic structure within these lines not shown by multilocus typing, and suggests that drug resistance has emerged multiple times in this closely related set of lines. Sequence comparisons with other Leishmania species and analysis of single-nucleotide diversity within our sample showed evidence of selection acting in a range of surface- and transport-related genes, including genes associated with drug resistance. Against a background of relative genetic homogeneity, we found extensive variation in chromosome copy number between our lines. Other forms of structural variation were significantly associated with drug resistance, notably including gene dosage and the copy number of an experimentally verified circular episome present in all lines and described here for the first time. This study provides a basis for more powerful molecular profiling of visceral leishmaniasis, providing additional power to track the drug resistance and epidemiology of an important human pathogen.

Indexed as

Gene DosageGenes, ProtozoanBase SequenceDrug ResistanceHumansLeishmania donovaniLeishmaniasis, VisceralMolecular Sequence DataSequence Analysis, DNASpecies Specificity

Identifiers

PMID22038251
PMCPMC3227103
OpenAlexW2144120140

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.