Abstract:
:Genetic surveillance of malaria parasites supports malaria control programmes, treatment guidelines and elimination strategies. Surveillance studies often pose questions about malaria parasite ancestry (e.g. how antimalarial resistance has spread) and employ statistical methods that characterise parasite population structure. Many of the methods used to characterise structure are unsupervised machine learning algorithms which depend on a genetic distance matrix, notably principal coordinates analysis (PCoA) and hierarchical agglomerative clustering (HAC). PCoA and HAC are sensitive to both the definition of genetic distance and algorithmic specification. Importantly, neither algorithm infers malaria parasite ancestry. As such, PCoA and HAC can inform (e.g. via exploratory data visualisation and hypothesis generation), but not answer comprehensively, key questions about malaria parasite ancestry. We illustrate the sensitivity of PCoA and HAC using 393 Plasmodium falciparum whole genome sequences collected from Cambodia and neighbouring regions (where antimalarial resistance has emerged and spread recently) and we provide tentative guidance for the use and interpretation of PCoA and HAC in malaria parasite genetic epidemiology. This guidance includes a call for fully transparent and reproducible analysis pipelines that feature (i) a clearly outlined scientific question; (ii) a clear justification of analytical methods used to answer the scientific question along with discussion of any inferential limitations; (iii) publicly available genetic distance matrices when downstream analyses depend on them; and (iv) sensitivity analyses. To bridge the inferential disconnect between the output of non-inferential unsupervised learning algorithms and the scientific questions of interest, tailor-made statistical models are needed to infer malaria parasite ancestry. In the absence of such models speculative reasoning should feature only as discussion but not as results.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Watson JA,Taylor AR,Ashley EA,Dondorp A,Buckee CO,White NJ,Holmes CCdoi
10.1371/journal.pgen.1009037subject
Has Abstractpub_date
2020-10-09 00:00:00pages
e1009037issue
10eissn
1553-7390issn
1553-7404pii
PGENETICS-D-20-00579journal_volume
16pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Third-generation cephalosporins are a class of β-lactam antibiotics that are often used for the treatment of human infections caused by Gram-negative bacteria, especially Escherichia coli. Worryingly, the incidence of human infections caused by third-generation cephalosporin-resistant E. coli is increasing worldwide. ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004776
更新日期:2014-12-18 00:00:00
abstract::Checkpoint pathways regulate genomic integrity in part by blocking anaphase until all chromosomes have been completely replicated, repaired, and correctly aligned on the spindle. In Saccharomyces cerevisiae, DNA damage and mono-oriented or unattached kinetochores trigger checkpoint pathways that bifurcate to regulate ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002176
更新日期:2011-07-01 00:00:00
abstract::Reproductive proteins are among the fastest evolving in the proteome, often due to the consequences of positive selection, and their rapid evolution is frequently attributed to a coevolutionary process between interacting female and male proteins. Such a process could leave characteristic signatures at coevolving gene...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000570
更新日期:2009-07-01 00:00:00
abstract::Genome-wide association studies (GWAS) have become increasingly common due to advances in technology and have permitted the identification of differences in single nucleotide polymorphism (SNP) alleles that are associated with diseases. However, while typical GWAS analysis techniques treat markers individually, comple...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002101
更新日期:2011-06-01 00:00:00
abstract::Evolutionary life history theory seeks to explain how reproductive and survival traits are shaped by selection through allocations of an individual's resources to competing life functions. Although life-history traits evolve rapidly, little is known about the genetic and cellular mechanisms that control and couple the...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006219
更新日期:2016-07-28 00:00:00
abstract::DNA mismatch repair greatly increases genome fidelity by recognizing and removing replication errors. In order to understand how this fidelity is maintained, it is important to uncover the relative specificities of the different components of mismatch repair. There are two major mispair recognition complexes in eukary...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003920
更新日期:2013-10-01 00:00:00
abstract::Faithful replication and repair of DNA lesions ensure genome maintenance. During replication in eukaryotic cells, DNA is unwound by the CMG helicase complex, which is composed of three major components: the Cdc45 protein, Mcm2-7, and the GINS complex. The CMG in complex with DNA polymerase epsilon (CMG-E) participates...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008494
更新日期:2019-12-09 00:00:00
abstract::Cooperative transcription factor binding at cis-regulatory sites in the genome drives robust eukaryotic gene expression, and many such sites must be coordinated to produce coherent transcriptional programs. The transcriptional program leading to motile cilia formation requires members of the DNA-binding forkhead (Fox)...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006538
更新日期:2017-01-19 00:00:00
abstract::In the last two decades, mitochondrial DNA (mtDNA) and the non-recombining portion of the Y chromosome (NRY) have been extensively used in order to measure the maternally and paternally inherited genetic structure of human populations, and to infer sex-specific demography and history. Most studies converge towards the...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000200
更新日期:2008-09-26 00:00:00
abstract::Genetic variants in genome-wide association studies (GWAS) are tested for disease association mostly using simple regression, one variant at a time. Standard approaches to improve power in detecting disease-associated SNPs use multiple regression with Bayesian variable selection in which a sparsity-enforcing prior on ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007856
更新日期:2018-12-31 00:00:00
abstract::Adult skeletal muscles are maintained during homeostasis and regenerated upon injury by muscle stem cells (MuSCs). A heterogeneity in self-renewal, differentiation and regeneration properties has been reported for MuSCs based on their anatomical location. Although MuSCs derived from extraocular muscles (EOM) have a hi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1009022
更新日期:2020-10-30 00:00:00
abstract::We recently discovered a secreted and diffusible midline cue called MADD-4 (an ADAMTSL) that guides migrations along the dorsoventral axis of the nematode Caenorhabditis elegans. We showed that the transmembrane receptor, UNC-40 (DCC), whose canonical ligand is the UNC-6 (netrin) guidance cue, is required for extensio...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004521
更新日期:2014-08-14 00:00:00
abstract::One of the striking findings of comparative developmental genetics was that expression patterns of core transcription factors are extraordinarily conserved in bilaterians. However, it remains unclear whether cis-regulatory elements of their target genes also exhibit common signatures associated with conserved embryoni...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000912
更新日期:2010-04-15 00:00:00
abstract::Methylcytosine-binding proteins decipher the epigenetic information encoded by DNA methylation and provide a link between DNA methylation, modification of chromatin structure, and gene silencing. VARIANT IN METHYLATION 1 (VIM1) encodes an SRA (SET- and RING-associated) domain methylcytosine-binding protein in Arabidop...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000156
更新日期:2008-08-15 00:00:00
abstract::Genotoxic agents that cause double-strand breaks (DSBs) often generate damage at the break termini. Processing enzymes, including nucleases and polymerases, must remove damaged bases and/or add new bases before completion of repair. Artemis is a nuclease involved in mammalian nonhomologous end joining (NHEJ), but in S...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000060
更新日期:2008-04-25 00:00:00
abstract::DNA double-strand breaks (DSBs) are one of the most dangerous DNA lesions, since their erroneous repair by nonhomologous end-joining (NHEJ) can generate harmful chromosomal rearrangements. PolX DNA polymerases are well suited to extend DSB ends that cannot be directly ligated due to their particular ability to bind to...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003656
更新日期:2013-01-01 00:00:00
abstract::Studies of synthetic, well-defined biomolecular systems can elucidate inherent capabilities that may be difficult to uncover in a native biological context. Here, we used a minimal, reconstituted translation system from Escherichia coli to identify efficient ribosome binding sites (RBSs) in an unbiased, high-throughpu...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002598
更新日期:2012-01-01 00:00:00
abstract::Craniofacial abnormalities, including facial skeletal defects, comprise approximately one-third of all birth defects in humans. Since most bones in the face derive from cranial neural crest cells (CNCCs), which are multipotent stem cells, craniofacial bone disorders are largely attributed to defects in CNCCs. However,...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007340
更新日期:2018-05-02 00:00:00
abstract::For many genes, proper gene expression requires coordinated and dynamic interactions between multiple regulatory elements, each of which can either promote or silence transcription. In Drosophila, the complexity of the regulatory landscape is further complicated by the tight physical pairing of homologous chromosomes,...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008152
更新日期:2019-05-10 00:00:00
abstract::How do adapting populations navigate the tensions between the costs of gene expression and the benefits of gene products to optimize the levels of many genes at once? Here we combined independently-arising beneficial mutations that altered enzyme levels in the central metabolism of Methylobacterium extorquens to uncov...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004149
更新日期:2014-02-27 00:00:00
abstract::Efficient adaptation to iron starvation is an essential virulence determinant of the most common human mold pathogen, Aspergillus fumigatus. Here, we demonstrate that the cytosolic monothiol glutaredoxin GrxD plays an essential role in iron sensing in this fungus. Our studies revealed that (i) GrxD is essential for gr...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008379
更新日期:2019-09-16 00:00:00
abstract::In nature, microbes often need to "decide" which of several available nutrients to utilize, a choice that depends on a cell's inherent preference and external nutrient levels. While natural environments can have mixtures of different nutrients, phenotypic variation in microbes' decisions of which nutrient to utilize i...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006766
更新日期:2017-05-24 00:00:00
abstract::Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disease with high penetrance, manifest by brain hemorrhages in young normotensive adults. In Iceland, this condition is caused by the L68Q mutation in the cystatin C gene, with contemporary carriers reaching an average age of only 30 years. Here...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000099
更新日期:2008-06-20 00:00:00
abstract::Ubiquitination of the replication clamp proliferating cell nuclear antigen (PCNA) at the conserved residue lysine (K)164 triggers postreplicative repair (PRR) to fill single-stranded gaps that result from stalled DNA polymerases. However, it has remained elusive as to whether cells engage PRR in response to replicatio...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005659
更新日期:2015-11-06 00:00:00
abstract::Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biol...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001296
更新日期:2011-02-10 00:00:00
abstract::Recently, Wu and colleagues [1] proposed two novel statistics for genome-wide interaction analysis using case/control or case-only data. In computer simulations, their proposed case/control statistic outperformed competing approaches, including the fast-epistasis option in PLINK and logistic regression analysis under ...
journal_title:PLoS genetics
pub_type: 评论,杂志文章
doi:10.1371/journal.pgen.1002625
更新日期:2012-01-01 00:00:00
abstract::Gap junctions are present in both vertebrates and invertebrates from nematodes to mammals. Although the importance of gap junctions has been documented in many biological processes, the molecular mechanisms underlying gap junction dynamics remain unclear. Here, using the C. elegans PLM neurons as a model, we show that...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005948
更新日期:2016-03-25 00:00:00
abstract::Neurofibromatosis type 1 is a monogenetic disorder that predisposes individuals to tumor formation and cognitive and behavioral symptoms. The neuronal circuitry and developmental events underlying these neurological symptoms are unknown. To better understand how mutations of the underlying gene (NF1) drive behavioral ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008920
更新日期:2020-07-22 00:00:00
abstract::In all sexually reproducing organisms, cells of the germ line must transition from mitosis to meiosis. In mice, retinoic acid (RA), the extrinsic signal for meiotic initiation, activates transcription of Stra8, which is required for meiotic DNA replication and the subsequent processes of meiotic prophase. Here we repo...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004541
更新日期:2014-08-07 00:00:00
abstract::Genome-wide association studies (GWAS) have now been conducted for hundreds of phenotypes of relevance to human health. Many such GWAS involve multiple closely-related phenotypes collected on the same samples. However, the vast majority of these GWAS have been analyzed using simple univariate analyses, which consider ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008431
更新日期:2019-10-09 00:00:00