Recurrence is a hallmark of cancer-driving mutations. Recurrent mutations can arise at the same site or affect the same gene at different sites. Here we identified a set of mutations arising in individual samples and altering different cis-regulatory elements that converge on a common gene via chromatin interactions. The mutations and genes identified in this fashion showed strong relevance to cancer, in contrast to noncoding mutations with site-specific recurrence only. We developed a prediction method that identifies potentially recurrent mutations on the basis of the features shared by mutations whose recurrence is observed in a given cohort. Our method was capable of accurately predicting recurrent mutations at the level of target genes but not mutations recurring at the same site. We experimentally validated predicted mutations in distal regulatory regions of the TERT gene. In conclusion, we propose a novel approach to discovering potential cancer-driving mutations in noncoding regions.
The recent advances of wearable sensors are remarkable but there are still limitations that they need to be refabricated to tune the sensor for target signal. However, biological sensory systems have the inherent potential to adjust their sensitivity according to the external environment, allowing for a broad and enhanced detection. Here, we developed a Tunable, Ultrasensitive, Nature-inspired, Epidermal Sensor (TUNES) that the strain sensitivity was dramatically increased (GF ~30k) and the pressure sensitivity could be tuned (10–254 kPa−1) by preset membrane tension. The sensor adjusts the sensitivity to the pressure regime by preset tension, so it can measure a wide range (0.05 Pa–25 kPa) with the best performance: from very small signals such as minute pulse to relatively large signals such as muscle contraction and respiration. We verified its capabilities as a wearable health monitoring system by clinical trial comparing with pressure wire which is considered the current gold standard of blood pressure (r = 0.96) and home health care system by binary classification of Old’s/Young’s pulse waves via machine learning (accuracy 95%).
BackgroundOne of the greatest challenges in cancer genomics is to distinguish driver mutations from passenger mutations. Whereas recurrence is a hallmark of driver mutations, it is difficult to observe recurring noncoding mutations owing to a limited amount of whole-genome sequenced samples. Hence, it is required to develop a method to predict potentially recurrent mutations.ResultsIn this work, we developed a random forest classifier that predicts regulatory mutations that may recur based on the features of the mutations repeatedly appearing in a given cohort. With breast cancer as a model, we profiled 35 quantitative features describing genetic and epigenetic signals at the mutation site, transcription factors whose binding motif was disrupted by the mutation, and genes targeted by long-range chromatin interactions. A true set of mutations for machine learning was generated by interrogating publicly available pan-cancer genomes based on our statistical model of mutation recurrence. The performance of our random forest classifier was evaluated by cross validations. The variable importance of each feature in the classification of mutations was investigated. Our statistical recurrence model for the random forest classifier showed an area under the curve (AUC) of ~0.78 in predicting recurrent mutations. Chromatin accessibility at the mutation sites, the distance from the mutations to known cancer risk loci, and the role of the target genes in the regulatory or protein interaction network were among the most important variables.ConclusionsOur methods enable to characterize recurrent regulatory mutations using a limited number of whole-genome samples, and based on the characterization, to predict potential driver mutations whose recurrence is not found in the given samples but likely to be observed with additional samples.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1385-y) contains supplementary material, which is available to authorized users.
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