Cancer cells display complex genomic aberrations that include large-scale genetic rearrangements and epigenetic modulation that are not easily characterized by short-read sequencing. We present a method for simultaneous profiling of long-range genetic/epigenetic changes in matched cancer samples. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer. Most ccRCC cases demonstrate somatic genomic alterations involving the short arm of chromosome 3 (3p), most often targeting the von Hippel-Lindau (VHL) gene. Aiming to identify somatic alterations that characterize early stage ccRCC, we performed comprehensive genetic, cytogenetic and epigenetic analyses comparing ccRCC tumor to adjacent non-tumorous tissue. Optical genome mapping identified genomic aberrations such as structural and copy number variations, complementing exome-sequencing results. Single-molecule methylome and hydroxymethylome mapping revealed multiple differential regions, some of them known to be associated with ccRCC pathogenesis. Among them, metabolic pathways were significantly enriched. Moreover, significant global epigenetic differences were detected between the tumor and the adjacent non-tumorous tissue, and a correlation between epigenetic signals and gene expression was found. This is the first reported comparison of a human tumor and a matched tissue by optical genome/epigenome mapping, revealing well-established and novel somatic aberrations.

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Adsorption is the accumulation of a solute at an interface that is formed between a solution and an additional gas, liquid, or solid phase. The macroscopic theory of adsorption dates back more than a century and is now well-established. Yet, despite recent advancements, a detailed and self-contained theory of \textit{single-particle adsorption} is still lacking. Here, we bridge this gap by developing a microscopic theory of adsorption kinetics, from which the macroscopic properties follow directly. One of our central achievements is the derivation of the microsopic version of the seminal Ward-Tordai relation, which connects the surface and subsurface adsorbate concentrations via a universal equation that holds for arbitrary adsorption dynamics. Furthermore, we present a microscopic interpretation of the Ward-Tordai relation which, in turn, allows us to generalize it to arbitrary dimension, geometry and initial conditions. The power of our approach is showcased on a set of hitherto unsolved adsorption problems to which we present exact analytical solutions. The framework developed herein sheds fresh light on the fundamentals of adsorption kinetics, which opens new research avenues in surface science with applications to artificial and biological sensing and to the design of nano-scale devices.

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How much time does it take for two molecules to react? If a reaction occurs upon contact, the answer to this question boils down to the classic first-passage time problem: find the time it takes for the two molecules to meet. However, this is not always the case as molecules switch stochastically between reactive and non-reactive states. The reaction is then said to be “gated” by the internal states of the molecules involved, which could have a dramatic influence on kinetics. A unified, continuous-time, approach to gated reactions on networks was presented in a recent paper [Scher and Reuveni, Phys. Rev. Lett. 127, 018301 (2021)]. Here, we build on this recent advancement and develop an analogous discrete-time version of the theory. Similar to continuous-time, we employ a renewal approach to show that the gated reaction time can always be expressed in terms of the corresponding ungated first-passage and return times, which yields formulas for the generating function of the gated reaction-time distribution and its corresponding mean and variance. In cases where the mean reaction time diverges, we show that the long-time asymptotics of the gated problem is inherited from its ungated counterpart. However, when molecules spend most of their time non-reactive, an interim regime of slower power-law decay emerges prior to the terminal asymptotics. The discretization of time also gives rise to resonances and anti-resonances, which were absent from the continuous-time picture. These features are illustrated using two case studies that also demonstrate how the general approach presented herein greatly simplifies the analysis of gated reactions.