Biology subjects

Hoh, C.

Publications and source records attributed to Hoh, C..

3 recordsLinked to original sources

bioRxiv2024

Combining DNA and protein alignments to improve genome annotation with LiftOn

As the number and variety of assembled genomes continues to grow, the number of annotated genomes is falling behind, particularly for eukaryotes. DNA-based mapping tools help to address this challenge, but they are only able to transfer annotation between closely-related species. Here we introduce LiftOn, a homology-based software tool that integrates DNA and protein alignments to enhance the accuracy of genome-scale annotation and to allow mapping between relatively distant species. LiftOns protein-centric algorithm considers both types of alignments, chooses optimal open reading frames, resolves overlapping gene loci, and finds additional gene copies where they exist. LiftOn can reliably transfer annotation between genomes representing members of the same species, as we demonstrate on human, mouse, honey bee, rice, and Arabidopsis thaliana. It can further map annotation effectively across species pairs as far apart as mouse and rat or Drosophila melanogaster and D. erecta.

bioinformatics↗

bioRxiv2024

Discovering Intron Gain Events in Humans through Large-Scale Evolutionary Comparisons

The rapid growth in the number of sequenced genomes makes it possible to search for the appearance of entirely new introns in the human lineage. In this study, we compared the genomic sequences for 19,120 human protein-coding genes to a collection of 3493 vertebrate genomes, mapping the patterns of intron alignments onto a phylogenetic tree. This mapping allowed us to trace many intron gain events to precise locations in the tree, corresponding to distinct points in evolutionary history. We discovered 584 intron gain events, all of them relatively recent, in 514 distinct human genes. Among these events, we explored the hypothesis that intronization was the mechanism responsible for intron gain. Intronization events were identified by locating instances where human introns correspond to exonic sequences in homologous vertebrate genes. Although apparently rare, we found three compelling cases of intronization, and for each of those we compared the human protein sequence and structure to homologous genes that lack the introns.

evolutionary biology↗

bioRxiv2021

MicroPET evidence for a hypersensitive neuroinflammatory profile of gp120 mouse model of HIV

Despite increased survivability for people living with HIV (PLWH), HIV-related cognitive and behavioral abnormalities persist. Determining the biological mechanism(s) underlying these abnormalities is critical to minimize the long-term impact of HIV. Human positron emission tomography (PET) studies reveal that PLWH exhibit higher neuroinflammation, which may contribute to cognitive and behavioral problems. PLWH are hypersensitive to environmental insults that drive elevated inflammatory profiles. Gp120 is an envelope glycoprotein exposed on the surface of the HIV envelope which enables HIV virus entry into a cell and contributes to HIV-related neurotoxicity. Gp120 overexpression in mice enables delineating its impact, including on neuroinflammation. In vivo evidence for gp120 transgenic (Tg) mice exhibiting neuroinflammation has yet to be determined. Here, we conducted microPET imaging in male gp120 Tg and wildtype mice, using the radiotracer [(18)F]FEPPA which binds to the translocator protein expressed by activated microglial and serves as a marker of neuroinflammation. Imaging was performed at baseline and 24 hours after treatment with lipopolysaccharide (LPS; 5 mg/kg), endotoxin that triggers an immune response. Gp120 Tg mice exhibited elevated [(18F)]FEPPA in response to LPS vs. wildtype mice throughout the brain including dorsal and ventral striata, hypothalamus, and hippocampus, but not prefrontal cortex. Gp120 Tg mice are hypersensitive to environmental inflammatory insults, consistent with PLWH, measurable in vivo. It remains to-be-determined whether this heightened sensitivity is connected to the behavioral abnormalities of these mice or is sensitive to antiretroviral or other treatments.

neuroscience↗