Long-read sequencing technologies offer the potential to capture multiple RNA processing events within single molecules, but standard protocols suffer from quantification biases and sequencing errors that limit their utility for precise analysis. Here, we describe Long-read 3′ RACE-seq (L3R-seq), a targeted long-read sequencing method that ligates a unique molecular identifier (UMI)-containing adapter to the 3′ […]
OpenSplice: the impact of half a million mutations on the alternative splicing of 600 human exons
Alternative splicing of mRNA precursors is an important step in gene regulation and a major mechanism by which genetic variants cause human disease. However, changes in splicing have only been quantified for a tiny fraction of possible variants in the human genome, limiting our ability to interpret clinical variants, evaluate and develop machine learning models, […]
Bayesian Estimation of Mosaic Loss of Chromosome Y from Bulk RNA Sequencing Data
Mosaic loss of chromosome Y (LOY) is a common age-associated somatic alteration in men and is typically measured from DNA-based assays. Many cohorts, however, contain bulk RNA-seq data without matched DNA-based LOY measurements. We developed a Bayesian framework to estimate the fraction of cells with LOY from male bulk RNA-seq by modeling reduced Y-linked gene […]
Protein-level prediction of Klebsiella phage adsorption identifies conserved receptor-binding motifs.
Bacteriophage therapy offers a potential route to treat antibiotic-resistant Klebsiella pneumoniae infections, but its use is limited by the narrow specificity of phage-host interactions. In Klebsiella, adsorption is largely determined by receptor-binding proteins (RBPs) that recognize bacterial capsular polysaccharides, yet current machine learning approaches often represent whole phages rather than the individual proteins that mediate […]
Mu-opioid receptor expression across cell-type specific afferents to the ventral tegmental area in male mice.
The addictive properties of opioids are due in part to these drugs ability to alter ventral tegmental area (VTA) activity via activation of mu opioid receptors (MORs) on local and distal inputs. Prior studies have identified numerous possible opioid-modulated afferents to the VTA, but the degree to which they express these receptors is not known. […]
Molecular underpinning of Hydra viridissima-algal facultative symbiosis and vertical algal transmission
The symbiosis between algae and animals represents a relatively recent evolutionary innovation, and exemplified by species in the Cnidaria phylum. Cnidaria can harbor algae within a modified cellular organelle called the symbiosome in a process called endosymbiosis. This animal-algal symbiosis can be facultative or obligate. Algae acquisition occurs either by horizontal transmission, where free-swimming planula […]
Does the sequence of a disordered protein encode small molecule binding paths?
Ligand binding to intrinsically disordered proteins resists description in terms of conventional binding pockets, yet it can be analysed as a dynamic process in which ligands move across transient surface interaction sites. Here we characterise a pathway-based representation in which ligand binding is described as a sequence of transitions between residue-defined microstates, enabling ligand-specific effects […]
Environmental DNA analysis to search for an endangered desert fish
We conducted field surveys over two consecutive years (2022 and 2023) of freshwater habitats in the Rio De La Concepcion (several tributaries and sites) and one site in the Rio Santa Cruz (tributary of the Gila River) in the state of Sonora, Mexico. Our primary goal was to detect the presence of the Rio Concepcion […]
Thalamic input drives co-timed excitation and inhibition to suppress cortical neuronal variability during movement initiation
Cortical activity is inherently dynamic, with ongoing fluctuations introducing variability into sensory-to-motor transformations. During movement initiation, neural variability in the motor cortex is sharply reduced, or ‘quenched’, a general phenomenon thought to ensure reliable population responses across cortical areas. However, the synaptic and circuit-level basis for this reduction in neural variability remains unclear. Here, we […]
The effects of group size and assortment on the evolution of division of labor
Stable variation in public-good production can generate biological division of labor. Two key drivers are the size of interacting groups and the degree of assortment (relatedness) among individuals with similar investment levels. Here we extend adaptive-dynamic models of continuous public-goods investment by allowing assortment in group formation. We show that increasing group size typically enlarges […]
Spatiotemporal Dynamics of Highly Pathogenic Avian Influenza H5 Virus Introductions and Regional Spread in the Republic of Korea
Highly pathogenic avian influenza (HPAI) viruses from clade 2.3.4.4 have caused recurrent outbreaks in poultry since 2014. In the Republic of Korea, clade 2.3.4.4b viruses have driven five epidemic waves, yet the factors underlying HPAI introduction and farm-to-farm spread remain poorly understood. We compiled hemagglutinin gene sequences of clade 2.3.4.4b viruses from wild birds and […]
Growth bistability in small bacterial populations exposed to antibiotics
With the development of microfluidics, it has now become possible to assess the susceptibility of bacteria to antibiotics at the single-cell level instead of relying on population measurements. Such studies are particularly relevant when the growth of bacterial population in the presence of antibiotics is heterogeneous. Here, we build a model to describe such a […]