Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Bistability and explosive transients in surface reactions: the role of fluctuations and spatial correlations

We study the dynamics of a class of catalytic surface reactions in which an adsorbed molecule undergoes dissociation giving oxygen, which then rapidly reacts with H adatoms to give water. The reaction-diffusion equations predict bistability and explosive transients similar to those observed in several low-pressure experiments. Kinetic Monte Carlo simulations reveal however that the dynamics can be strongly affected by spontaneous, inhomogeneous fluctuations of composition on the surface. In particular, bifurcation points can be displaced and the explosive character of the transients can be lost, depending on a subtle balance between the rate of reaction and the mobility of the decomposing species. These effects can be quantified on the basis of a stochastic formulation of the dynamics taking into account spatial correlations. This approach allows to better delimit the applicability of the traditional reaction-diffusion modelling in the case of reactions such as the reduction of NO x or SO x species on catalytic surfaces. © 2010 EDP Sciences, Società Italiana di Fisica, Springer-Verlag.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A mitochondria-specific mutational signature of aging: increased rate of A > G substitutions on the heavy strand.

The mutational spectrum of the mitochondrial DNA (mtDNA) does not resemble any of the known mutational signatures of the nuclear genome and variation in mtDNA mutational spectra between different organisms is still incomprehensible. Since mitochondria are responsible for aerobic respiration, it is expected that mtDNA mutational spectrum is affected by oxidative damage. Assuming that oxidative damage increases with age, we analyse mtDNA mutagenesis of different species in regards to their generation length. Analysing, (i) dozens of thousands of somatic mtDNA mutations in samples of different ages (ii) 70053 polymorphic synonymous mtDNA substitutions reconstructed in 424 mammalian species with different generation lengths and (iii) synonymous nucleotide content of 650 complete mitochondrial genomes of mammalian species we observed that the frequency of AH > GH substitutions (H: heavy strand notation) is twice bigger in species with high versus low generation length making their mtDNA more AH poor and GH rich. Considering that AH > GH substitutions are also sensitive to the time spent single-stranded (TSSS) during asynchronous mtDNA replication we demonstrated that AH > GH substitution rate is a function of both species-specific generation length and position-specific TSSS. We propose that AH > GH is a mitochondria-specific signature of oxidative damage associated with both aging and TSSS