Background: Cellular senescence is accompanied by extensive epigenomic reprogramming leading to changes in enhancer RNA levels, yet how enhancer activity is translated into functional RNA-level regulation remains unclear. Here we investigate how enhancer reprogramming during senescence impacts functional RNA-level regulation by eRNAs. Results: By integrating time-resolved transcriptomic analyses across multiple primary human cell types, we […]
Adaptive receptor expression and the emergence of disease as loss of signaling homeostasis
Our bodies have evolved to maintain homeostasis through regulatory systems that continuously adapt to keep physiological processes within a normal range. From this perspective, complex chronic disease can be understood as a breakdown of compensatory mechanisms, resulting in loss of homeostasis. Here we propose that adaptive receptor expression dynamics may serve as one such compensatory […]
LongcallD: joint calling and phasing of small, structural and mosaic variants from long reads
Long-read sequencing is a powerful technique capturing multiple variants within single continuous reads. This length allows individual reads to bridge small and structural variants while carrying crucial phasing information. However, current computational tools treat small variant calling, structural variant (SV) detection and phasing as largely disconnected problems, failing to unleash the full potential of long […]
Evolutionary and functional genomics reveal that Ralstonia wilt pathogens actively deploy antimicrobial warfare while leveraging physiological adaptations during plant infection
The xylem pathogens in the Ralstonia solanacearum species complex (RSSC) cause wilt diseases that threaten global food security. These diverse pathogens are highly adapted to the in planta environment where they proliferate and cause rapid, aggressive diseases. To understand the genetic underpinnings of these pathogens’ in planta fitness, we performed forward genetic screens in three […]
Diatom Endosymbionts have Shrinking but Stable Genomes Despite Low Coding Density
Successful establishment of long-term, obligate endosymbiotic relationships requires integration of hosts and endosymbionts across multiple levels. For example, highly integrated, host-beneficial endosymbionts typically have extremely reduced genomes and metabolisms. However, we do not yet fully understand the specific mechanisms that drive this integration or if there is a specific order in which these changes must […]
Additive Channels in Curved Fitness Landscapes
Additive genetic models often predict evolutionary change reasonably well, even though fitness landscapes can be curved and gene interactions are common. This paper explores one possible explanation: populations may frequently reside in regions of genetic space where local curvature contributes relatively little to fitness variation, so that linear predictions remain adequate. We call such regions […]