Biology subjects

Washington, N.

Publications and source records attributed to Washington, N..

4 recordsLinked to original sources

bioRxiv2025

A single-cell atlas of Toxoplasma sexual development identifies regulators of gametogenesis

Toxoplasma gondii undergoes sexual development exclusively in the feline intestine, a process critical for genetic diversity and population expansion. Recent studies have identified genes critical in suppressing presexual development and metabolic differences in felines that may promote sexual development, but to date the gene regulatory networks driving development in the cat are unknown. To investigate this, we performed single-cell transcriptomics on parasites isolated from cat intestines, using fluorescent reporter strains and flow cytometry. From 15,068 cells across two experiments, we identified rare populations, including cells that bear all of the hallmarks of gametes. Candidate genes emerging from this study were tested via CRISPR-Cas9 Perturb-seq, identifying AP2X6 as a regulator of macrogametocyte development. Our single-cell data extends what is known about gene expression changes throughout sexual development and should be useful to those in the field working towards inducing gametogenesis, mating, and oocyst production in vitro.

microbiology↗

bioRxiv2019

Population Health Genetic Screening for Tier 1 Inherited Diseases in Northern Nevada: 90% of At-Risk Carriers are Missed

In an unselected population of 23,713 participants who underwent clinical exome sequencing as a part of the Healthy Nevada Project (HNP) in Northern Nevada (Renown Health, Reno, Nevada) from March 15, 2018, to Sept 30, 2018 (Table S1) we find a 1.26% carrier rate for expected pathogenic and likely pathogenic genetic variants in (FH: LDLR, PCSK9, APOB), Hereditary Breast and Ovarian Cancer (HBOC: BRCA1, BRCA2) and Lynch Syndrome (LS: MLH1, MSH2, MSH6, PSM2) with over 90% of carriers undetected under current medical practice. 26% of carriers were found to have advanced disease with 70% first diagnosed before the age of 65. Less than 20% of all carriers had any documented suspicion for inherited genetic disease in the medical record and upon direct follow-up survey under 40% of carriers had family history of relevant disease. A population preventative genetic screening approach for patients under 45 may improve outcomes.\n\nO_TBL View this table:\norg.highwire.dtl.DTLVardef@1eb1896org.highwire.dtl.DTLVardef@19b2a11org.highwire.dtl.DTLVardef@1e6da81org.highwire.dtl.DTLVardef@1138699org.highwire.dtl.DTLVardef@e9c415_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable S1:C_FLOATNO O_TABLECAPTIONDemographic Profile of Healthy Nevada Project Participants.\n\nC_TABLECAPTION C_TBL

genetics↗

bioRxiv2017

Identifiers for the 21st century:How to design, provision, and reuse persistent identifiers to maximize utility and impact of life science data

In many disciplines, data is highly decentralized across thousands of online databases (repositories, registries, and knowledgebases). Wringing value from such databases depends on the discipline of data science and on the humble bricks and mortar that make integration possible; identifiers are a core component of this integration infrastructure. Drawing on our experience and on work by other groups, we outline ten lessons we have learned about the identifier qualities and best practices that facilitate large-scale data integration. Specifically, we propose actions that identifier practitioners (database providers) should take in the design, provision and reuse of identifiers; we also outline important considerations for those referencing identifiers in various circumstances, including by authors and data generators. While the importance and relevance of each lesson will vary by context, there is a need for increased awareness about how to avoid and manage common identifier problems, especially those related to persistence and web-accessibility/resolvability. We focus strongly on web-based identifiers in the life sciences; however, the principles are broadly relevant to other disciplines.

bioinformatics↗

bioRxiv2016

The Monarch Initiative: Insights across species reveal human disease mechanisms

The principles of genetics apply across the whole tree of life: on a cellular level, we share mechanisms with species from which we diverged millions or even billions of years ago. We can exploit this common ancestry at the level of sequences, but also in terms of observable outcomes (phenotypes), to learn more about health and disease for humans and all other species. Applying the range of available knowledge to solve challenging disease problems requires unified data relating genomics, phenotypes, and disease; it also requires computational tools that leverage these multimodal data to inform interpretations by geneticists and to suggest experiments. However, the distribution and heterogeneity of databases is a major impediment: databases tend to focus either on a single data type across species, or on single species across data types. Although each database provides rich, high-quality information, no single one provides unified data that is comprehensive across species, biological scales, and data types. Without a big-picture view of the data, many questions in genetics are difficult or impossible to answer. The Monarch Initiative (https://monarchinitiative.org) is an international consortium dedicated to providing computational tools that leverage a computational representation of phenotypic data for genotype-phenotype analysis, genomic diagnostics, and precision medicine on the basis of a large-scale platform of multimodal data that is deeply integrated across species and covering broad areas of disease.

evolutionary biology↗