Dataset Information

Leishmania Sexual Reproductive Strategies as Resolved through Computational Methods Designed for Aneuploid Genomes.

ABSTRACT: A cryptic sexual reproductive cycle in Leishmania has been inferred through population genetic studies revealing the presence of hybrid genotypes in natural isolates, with attempts made to decipher sexual strategies by studying complex chromosomal inheritance patterns. A more informative approach is to study the products of controlled, laboratory-based experiments where known strains or species are crossed in the sand fly vector to generate hybrid progeny. These hybrids can be subsequently studied through high resolution sequencing technologies and software suites such as PAINT that disclose inheritance patterns including ploidies, parental chromosome contributions and recombinations, all of which can inform the sexual strategy. In this work, we discuss the computational methods in PAINT that can be used to interpret the sexual strategies adopted specifically by aneuploid organisms and summarize how PAINT has been applied to the analysis of experimental hybrids to reveal meiosis-like sexual recombination in Leishmania.

SUBMITTER: Shaik JS

PROVIDER: S-EPMC7912377 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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<i>Leishmania</i> Sexual Reproductive Strategies as Resolved through Computational Methods Designed for Aneuploid Genomes.

Shaik Jahangheer S JS Dobson Deborah E DE Sacks David L DL Beverley Stephen M SM

Genes 20210126 2

A cryptic sexual reproductive cycle in <i>Leishmania</i> has been inferred through population genetic studies revealing the presence of hybrid genotypes in natural isolates, with attempts made to decipher sexual strategies by studying complex chromosomal inheritance patterns. A more informative approach is to study the products of controlled, laboratory-based experiments where known strains or species are crossed in the sand fly vector to generate hybrid progeny. These hybrids can be subsequentl ...[more]

PMID: 33530584

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Project description:BackgroundMany of the 35 million women and girls aged 15-49 requiring humanitarian assistance have inadequate access to the sexual and reproductive health (SRH) services to which they are entitled. Ensuring accountability is critical to realizing their SRH and reproductive rights (RR).ObjectivesThis scoping review examines the extent and nature of existing evidence on accountability strategies for SRH in humanitarian settings in different geographical scopes/contexts, and contextualizes these findings in the larger thematic literature. This review seeks to answer the following questions: What accountability strategies are employed to address the availability, accessibility, acceptability, and quality of SRH in humanitarian settings? What do we know about the successes and challenges of the given strategies? What are the implications for practice?MethodsWe consulted public health, social science, and legal databases including SCOPUS, PubMed, ProQuest, and LexisNexis for peer-reviewed articles, as well as Google Advanced search for grey literature; the search was conducted in March 2019. We searched for relevant articles and documents relating to accountability, humanitarian, and SRH and/or RR. To identify key challenges not reflected in the literature and additional grey literature, 18 key informants from international NGOs, local government bodies, academia, and donor agencies were interviewed from March-June 2019.ResultsA total of 209 papers and documents were identified via our literature searches and interviews for review. We identified three categories of approaches to accountability in our background reading, and we then applied these to the papers reviewed a priori. We created a fourth category based on our findings. The categories include: (1) humanitarian principles, codes of conduct, and legal instruments; (2) technical, performance, and impact standards; (3) efforts to solicit and address the rights and needs of the affected populations, or "listening and responding," and, (4) accountability demands made by affected populations themselves. Almost all papers identified referred to challenges to realizing accountability in humanitarian contexts. There are promising accountability approaches - some specific to SRH and some not - such as open-ended feedback from affected populations, quality improvement, and practical application of standards. Reflecting a largely top down orientation, papers concentrate on accountability mechanisms within humanitarian work, with much less focus on supporting affected populations to deepen their understanding of structural causes of their position, understand their entitlements, or access justice.ConclusionIn the last 20 years, there has been increasing standard and guideline development and program experiences related to accountability in humanitarian settings. Yet, the emphasis is on tools or mechanisms for accountability with less attention to changing norms regarding SRH and RR within affected communities, and to a lesser extent, among implementers of humanitarian programs or to institutionalizing community participation.

Project description:The HeLa cell line was established in 1951 from cervical cancer cells taken from a patient, Henrietta Lacks. This was the first successful attempt to immortalize human-derived cells in vitro. The robust growth and unrestricted distribution of HeLa cells resulted in its broad adoption--both intentionally and through widespread cross-contamination--and for the past 60 years it has served a role analogous to that of a model organism. The cumulative impact of the HeLa cell line on research is demonstrated by its occurrence in more than 74,000 PubMed abstracts (approximately 0.3%). The genomic architecture of HeLa remains largely unexplored beyond its karyotype, partly because like many cancers, its extensive aneuploidy renders such analyses challenging. We carried out haplotype-resolved whole-genome sequencing of the HeLa CCL-2 strain, examined point- and indel-mutation variations, mapped copy-number variations and loss of heterozygosity regions, and phased variants across full chromosome arms. We also investigated variation and copy-number profiles for HeLa S3 and eight additional strains. We find that HeLa is relatively stable in terms of point variation, with few new mutations accumulating after early passaging. Haplotype resolution facilitated reconstruction of an amplified, highly rearranged region of chromosome 8q24.21 at which integration of the human papilloma virus type 18 (HPV-18) genome occurred and that is likely to be the event that initiated tumorigenesis. We combined these maps with RNA-seq and ENCODE Project data sets to phase the HeLa epigenome. This revealed strong, haplotype-specific activation of the proto-oncogene MYC by the integrated HPV-18 genome approximately 500 kilobases upstream, and enabled global analyses of the relationship between gene dosage and expression. These data provide an extensively phased, high-quality reference genome for past and future experiments relying on HeLa, and demonstrate the value of haplotype resolution for characterizing cancer genomes and epigenomes.

Dataset Information

Leishmania Sexual Reproductive Strategies as Resolved through Computational Methods Designed for Aneuploid Genomes.

Publications

<i>Leishmania</i> Sexual Reproductive Strategies as Resolved through Computational Methods Designed for Aneuploid Genomes.

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