An integrative approach for building personalized gene regulatory networks for precision medicine

Only a small fraction of patients respond to the drug prescribed to treat their disease, which means that most are at risk of unnecessary exposure to side effects through ineffective drugs. This inter-individual variation in drug response is driven by differences in gene interactions caused by each patient's genetic background, environmental exposures, and the proportions of specific cell types involved in disease. These gene interactions can now be captured by building gene regulatory networks, by taking advantage of RNA velocity (the time derivative of the gene expression state), the ability to study hundreds of thousands of cells simultaneously, and the falling price of single-cell sequencing. Here, we propose an integrative approach that leverages these recent advances in single-cell data with the sensitivity of bulk data to enable the reconstruction of personalized, cell-type- and context-specific gene regulatory networks. We expect this approach will allow the prioritization of key driver genes for specific diseases and will provide knowledge that opens new avenues towards improved personalized healthcare

Hope springs eternal in the starfish gonad: preserved potential for sexual reproduction in a single-clone population of a fissiparous starfish

Among echinoderms, asexual reproduction by fission occurs in few species. This strategy is considered a temporary response to stressful conditions and usually alternates with sexual reproduction events; thus, monoclonal populations are extremely rare. The occurrence of a single-clone population of the starfish Coscinasterias tenuispina at Llançà (NW Mediterranean) allowed us to study intra-clonal variation of the reproductive cycle during a two-year study. The few developed gonads (all male) were found in winter months, coinciding with the minimum photoperiod (ρ = −0.82; P < 0.001) and lowest temperatures (ρ = −0.75; P < 0.001), only in best-fed individuals, indicating that food availability influences individual ability for gonad development. Fissiparity happened throughout all the sampled period, but its rate increased with warm temperatures (ρ = 0.68; P < 0.0001). In contrast to what has been reported in other species, no correlation between fission rates and population density was found. The population was maintained over time by asexual reproduction and remained monoclonal. Although sexual reproduction has probably not occurred in this all-male population for a long time, the ability to yearly produce mature gonads is retained by some individuals, indicating that potential to reproduce sexually may be preserved, even in the case of strictly asexual populations