Resolving within-host malaria parasite diversity using single-cell sequencing

Malaria patients can carry one or more clonal lineage of the parasite, Plasmodium falciparum, but the composition of these infections cannot be directly inferred from bulk sequence data. Well-defined, complete haplotypes at single-cell resolution are ideal for describing within-host population structure and unambiguously determining parasite diversity, transmission dynamics and recent ancestry but have not been analyzed on a large scale. We generated 485 near-complete single-cell genome sequences isolated from fifteen P. falciparum patients from Chikhwawa, Malawi, an area of intense malaria transmission. Matched single-cell and bulk genomic analyses revealed patients harbored up to seventeen unique lineages. Estimation of parasite relatedness within patients suggests superinfection by repeated mosquito bites is rarer than co-transmission of parasites from a single mosquito. Our single-cell analysis indicates strong barriers to establishment of new infections in malaria-infected patients and allows high resolution dissection of intra-host variation in malaria parasites.

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Analysis of single-cell genome sequences of bacteria and archaea

Emerging Topics in Life Sciences ◽

10.1042/etls20160028 ◽

2017 ◽

Vol 1 (3) ◽

pp. 249-255 ◽

Cited By ~ 4

Author(s):

Robert M. Bowers ◽

Devin F.R. Doud ◽

Tanja Woyke

Keyword(s):

Single Cell ◽

Genome Sequencing ◽

Genome Analysis ◽

Sequence Data ◽

Bacterial Cells ◽

Genome Sequences ◽

Genetic Makeup ◽

Cell Genome ◽

Uncultured Microorganisms ◽

Single Cell Genome

Single-cell genome sequencing of individual archaeal and bacterial cells is a vital approach to decipher the genetic makeup of uncultured microorganisms. With this review, we describe single-cell genome analysis with a focus on the unique properties of single-cell sequence data and with emphasis on quality assessment and assurance.

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Resource: Scalable whole genome sequencing of 40,000 single cells identifies stochastic aneuploidies, genome replication states and clonal repertoires

10.1101/411058 ◽

2018 ◽

Cited By ~ 8

Author(s):

Emma Laks ◽

Hans Zahn ◽

Daniel Lai ◽

Andrew McPherson ◽

Adi Steif ◽

...

Keyword(s):

Single Cell ◽

Genome Sequencing ◽

Large Scale ◽

Single Cells ◽

Genome Structure ◽

Cancer Tissue ◽

Genome Replication ◽

Wide Range ◽

Cell Genome ◽

Single Cell Genome

SummaryEssential features of cancer tissue cellular heterogeneity such as negatively selected genome topologies, sub-clonal mutation patterns and genome replication states can only effectively be studied by sequencing single-cell genomes at scale and high fidelity. Using an amplification-free single-cell genome sequencing approach implemented on commodity hardware (DLP+) coupled with a cloud-based computational platform, we define a resource of 40,000 single-cell genomes characterized by their genome states, across a wide range of tissue types and conditions. We show that shallow sequencing across thousands of genomes permits reconstruction of clonal genomes to single nucleotide resolution through aggregation analysis of cells sharing higher order genome structure. From large-scale population analysis over thousands of cells, we identify rare cells exhibiting mitotic mis-segregation of whole chromosomes. We observe that tissue derived scWGS libraries exhibit lower rates of whole chromosome anueploidy than cell lines, and loss of p53 results in a shift in event type, but not overall prevalence in breast epithelium. Finally, we demonstrate that the replication states of genomes can be identified, allowing the number and proportion of replicating cells, as well as the chromosomal pattern of replication to be unambiguously identified in single-cell genome sequencing experiments. The combined annotated resource and approach provide a re-implementable large scale platform for studying lineages and tissue heterogeneity.

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High-Quality Draft Single-Cell Genome Sequence Belonging to the Archaeal Candidate Division SA1, Isolated from Nereus Deep in the Red Sea

Genome Announcements ◽

10.1128/genomea.00383-18 ◽

2018 ◽

Vol 6 (19) ◽

pp. e00383-18 ◽

Cited By ~ 4

Author(s):

David K. Ngugi ◽

Ulrich Stingl

Keyword(s):

Single Cell ◽

Lake Sediments ◽

Red Sea ◽

Genome Sequence ◽

Soda Lake ◽

Genome Sequences ◽

High Quality ◽

Candidate Division ◽

Cell Genome ◽

Single Cell Genome

ABSTRACT Candidate division SA1 encompasses a phylogenetically coherent archaeal group ubiquitous in deep hypersaline anoxic brines around the globe. Recently, the genome sequences of two cultivated representatives from hypersaline soda lake sediments were published. Here, we present a single-cell genome sequence from Nereus Deep in the Red Sea that represents a putatively novel family within SA1.

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