Biology subjects

Ryon, K.

Publications and source records attributed to Ryon, K..

6 recordsLinked to original sources

bioRxiv2026

Modulator Resolves Transcript-, Allele-, and Condition-associated RNA Modification Differences from Direct RNA Sequencing

Nanopore direct-RNA sequencing (DRS) reports RNA modifications on single molecules, but there is no comprehensive algorithm for processing, aligning, and differentiating base modifications across reads that are often 5'-truncated. Here we present Modulator, which assigns every read, truncated or not, to a fragmentform, defined by a shared transcript 3'-end and the splice-junctions upstream of it. Of note, Modulator builds fragmentforms from genomic alignments without a reference transcriptome, estimates per-base modification stoichiometry within each fragmentform, and classifies each stoichiometry difference as transcript-, allele-, or condition-dependent. In the control HG002 transcriptome, Modulator built 23,746 fragmentforms, with 15,620 candidate novel isoforms that carried poly(A) signals as often as previously annotated transcripts. Also, assigning 5'-truncated reads to fragmentforms nearly doubled the number of testable and differentially modified sites. m6A sites within 100 nucleotides (nt) of a splice junction or within 1 kb of a poly(A) site were less modified in fragmentforms that use that junction or poly(A) site, indicating that local transcript context shapes where m6A is deposited. From the same reads, Modulator called SNPs with 93% precision and no phasing errors against the Genome in a Bottle benchmark. It identified 131 SNPs that create or remove a modifiable nucleotide and 1,358 allele-specific modification differences, most involving SNPs more than 50 nt from the modified site. In cells infected with Zika virus, which remodels gene expression relative to uninfected cells, Modulator identified 1,253 transcript-independent modification stoichiometry changes. Of the m6A changes at sites measured by GLORI, 96% agreed in direction with single-nucleotide-resolution GLORI maps of the same samples. Thus, Modulator accurately separates changes in RNA modification from transcript-associated and allele-associated differences and can improve the utility of nanopore DRS. Availability and Implementation: Modulator is free and open source: https://github.com/Theo-Nelson/Modulator. It is written in Python and runs on Linux OS.

bioinformatics↗

bioRxiv2026

Alternative polyadenylation drives isoform-dependent m6A remodeling during Zika virus infection

Alternative RNA processing generates extensive transcript diversity, yet how transcript architecture influences selective m6A deposition is incompletely understood. Exon-junction-based models explain where m6A is excluded, but a positive determinant of m6A accumulation remains undefined. Here, we leverage Zika virus-induced changes in m6A deposition to uncover determinants of transcript-selective methylation. By integrating GLORI-seq, native METTL3 RNA immunoprecipitation, and nanopore direct RNA sequencing, we generate a single-nucleotide, isoform-resolved map of m6A dynamics during infection. We identify over 2,000 dynamic m6A sites, many arising from changes in transcript architecture, and pinpoint proximal polyadenylation sites as positive determinants of m6A accumulation. The cleavage stimulation factors CSTF2 and CSTF2T drive this remodeling through two routes: redundant induction of intronic polyadenylation, which converts internal exons into terminal exons that expose DRACH motifs to METTL3, and non-redundant, cleavage-independent recruitment of METTL3 near proximal polyadenylation sites, establishing alternative polyadenylation as a key architectural determinant of the m6A landscape.

molecular biology↗

bioRxiv2023

Collection of Biospecimens from the Inspiration4 Mission Establishes the Standards for the Space Omics and Medical Atlas (SOMA)

The SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. Biospecimen samples were collected from the crew at different stages of the mission, including before (L-92, L-44, L-3 days), during (FD1, FD2, FD3), and after (R+1, R+45, R+82, R+194 days) spaceflight, creating a longitudinal sample set. The collection process included samples such as venous blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, SpaceX Dragon capsule HEPA filter, and skin biopsies, which were processed to obtain aliquots of serum, plasma, extracellular vesicles, and peripheral blood mononuclear cells. All samples were then processed in clinical and research laboratories for optimal isolation and testing of DNA, RNA, proteins, metabolites, and other biomolecules. This paper describes the complete set of collected biospecimens, their processing steps, and long-term biobanking methods, which enable future molecular assays and testing. As such, this study details a robust framework for obtaining and preserving high-quality human, microbial, and environmental samples for aerospace medicine in the Space Omics and Medical Atlas (SOMA) initiative, which can also aid future experiments in human spaceflight and space biology.

molecular biology↗

bioRxiv2022

Cross-kingdom metagenomic profiling of Lake Hillier reveals pigment-rich polyextremophiles and wide-ranging metabolic adaptations

Background Lake Hillier is a hypersaline lake known for its distinctive bright pink color. The cause of this phenomenon in other hypersaline sites has been attributed to halophiles, Dunaliella, and Salinibacter, however, a systematic analysis of the microbial communities, their functional features, and the prevalence of pigment-producing-metabolisms has not been previously studied. Our results are evidence that Lake Hillier is composed of a diverse set of microorganisms including archaea, bacteria, algae, and viruses. Our data indicate a core microbiome in Lake Hillier composed of multiple pigment-producer microbes, many of which are cataloged as polyextremophiles. Additionally, we estimated the diversity of metabolic pathways in the lake and determined that many of these are related to pigment production. We reconstructed complete or partial genomes for 21 discrete bacteria (N = 14) and archaea (N = 7), only 2 of which could be taxonomically annotated to previously observed species. Our findings provide the first metagenomic study to decipher the source of the pink color of Australias Lake Hillier. The study of this pink hypersaline environment is evidence of a microbial consortium of pigment producers, a repertoire of polyextremophiles, a core microbiome and potentially novel species.

microbiology↗

bioRxiv2020

Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, bacterial, and viral profiling. We applied both technologies across 857 SARS-CoV-2 clinical specimens and 86 NYC subway samples, providing a broad molecular portrait of the COVID-19 NYC outbreak. Our results define new features of SARS-CoV-2 evolution, nominate a novel, NYC-enriched viral subclade, reveal specific host responses in interferon, ACE, hematological, and olfaction pathways, and examine risks associated with use of ACE inhibitors and angiotensin receptor blockers. Together, these findings have immediate applications to SARS-CoV-2 diagnostics, public health, and new therapeutic targets.

molecular biology↗

bioRxiv2019

The Microbe Directory v2.0: An Expanded Database of Ecological and Phenotypical Features of Microbes.

The Microbe Directory (TMD) is a comprehensive database of annotations for microbial species collating features such as gram-stain, capsid-symmetry, resistance to antibiotics and more. This work presents a significant improvement to the original Microbe Directory (2018). This update adds 68,852 taxa, many new annotation features, an interface for the statistical analysis of microbiomes based on TMD features, and presents a portal for the broad community to add or correct entries. This update also adds curated lists of gene annotations which are useful for characterizing microbial genomes. Much of the new data in TMD is sourced from a set of databases and independent studies collating these data into a single quality controlled and curated source. This will allow researchers and clinicians to have easier access to microbial data and provide for the possibility of serendipitous discovery of otherwise unexpected trends.

microbiology↗