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SUMMARY: Deep mutational scanning (DMS) experiments provide a powerful method to measure the functional effects of genetic mutations at massive scales. However, the data generated from these experiments can be difficult to analyze, with significant variation between experimental replicates. To overcome this challenge, we developed popDMS, a computational method based on population genetics theory, to infer the functional effects of mutations from DMS data. Through extensive tests, we found that the functional effects of single mutations and epistasis inferred by popDMS are highly consistent across replicates, comparing favorably with existing methods. Our approach is flexible and can be widely applied to DMS data that includes multiple time points, multiple replicates, and different experimental conditions. AVAILABILITY AND IMPLEMENTATION: popDMS is implemented in Python and Julia, and is freely available on GitHub at https://github.com/bartonlab/popDMS.
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Mutação , Software , Epistasia Genética , Biologia Computacional/métodos , Genética Populacional/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise Mutacional de DNA/métodos , Humanos , AlgoritmosRESUMO
Epistasis refers to fitness or functional effects of mutations that depend on the sequence background in which these mutations arise. Epistasis is prevalent in nature, including populations of viruses, bacteria, and cancers, and can contribute to the evolution of drug resistance and immune escape. However, it is difficult to directly estimate epistatic effects from sampled observations of a population. At present, there are very few methods that can disentangle the effects of selection (including epistasis), mutation, recombination, genetic drift, and genetic linkage in evolving populations. Here we develop a method to infer epistasis, along with the fitness effects of individual mutations, from observed evolutionary histories. Simulations show that we can accurately infer pairwise epistatic interactions provided that there is sufficient genetic diversity in the data. Our method also allows us to identify which fitness parameters can be reliably inferred from a particular data set and which ones are unidentifiable. Our approach therefore allows for the inference of more complex models of selection from time-series genetic data, while also quantifying uncertainty in the inferred parameters.
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Epistasia Genética , Seleção Genética , Aptidão Genética , Ligação Genética , Modelos Genéticos , MutaçãoRESUMO
Deep mutational scanning (DMS) experiments provide a powerful method to measure the functional effects of genetic mutations at massive scales. However, the data generated from these experiments can be difficult to analyze, with significant variation between experimental replicates. To overcome this challenge, we developed popDMS, a computational method based on population genetics theory, to infer the functional effects of mutations from DMS data. Through extensive tests, we found that the functional effects of single mutations and epistasis inferred by popDMS are highly consistent across replicates, comparing favorably with existing methods. Our approach is flexible and can be widely applied to DMS data that includes multiple time points, multiple replicates, and different experimental conditions.
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Cervical cancer is a major health concern worldwide, highlighting the urgent need for better early detection methods to improve outcomes for patients. In this study, we present a novel digital pathology classification approach that combines Low-Rank Adaptation (LoRA) with the Vision Transformer (ViT) model. This method is aimed at making cervix type classification more efficient through a deep learning classifier that does not require as much data. The key innovation is the use of LoRA, which allows for the effective training of the model with smaller datasets, making the most of the ability of ViT to represent visual information. This approach performs better than traditional Convolutional Neural Network (CNN) models, including Residual Networks (ResNets), especially when it comes to performance and the ability to generalize in situations where data are limited. Through thorough experiments and analysis on various dataset sizes, we found that our more streamlined classifier is highly accurate in spotting various cervical anomalies across several cases. This work advances the development of sophisticated computer-aided diagnostic systems, facilitating more rapid and accurate detection of cervical cancer, thereby significantly enhancing patient care outcomes.
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Mosquito-borne disease remains a significant burden on global health. In the United States, the major threat posed by mosquitoes is transmission of arboviruses, including West Nile virus by mosquitoes of the Culex genus. Virus metagenomic analysis of mosquito small RNA using deep sequencing and advanced bioinformatic tools enables the rapid detection of viruses and other infecting organisms, both pathogenic and non-pathogenic to humans, without any precedent knowledge. In this study, we sequenced small RNA samples from over 60 pools of Culex mosquitoes from two major areas of Southern California from 2017 to 2019 to elucidate the virome and immune responses of Culex. Our results demonstrated that small RNAs not only allowed the detection of viruses but also revealed distinct patterns of viral infection based on location, Culex species, and time. We also identified miRNAs that are most likely involved in Culex immune responses to viruses and Wolbachia bacteria, and show the utility of using small RNA to detect antiviral immune pathways including piRNAs against some pathogens. Collectively, these findings show that deep sequencing of small RNA can be used for virus discovery and surveillance. One could also conceive that such work could be accomplished in various locations across the world and over time to better understand patterns of mosquito infection and immune response to many vector-borne diseases in field samples.
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Culex , Culicidae , Viroses , Humanos , Animais , Mosquitos Vetores , AntiviraisRESUMO
Recently, new devices combining two-dimensional (2D) materials with ferroelectrics, have been a new hotspot for promising applications in electronics and optoelectronics. Here, we design a new type of FET using the 2D MoS2 and poly(vinylidene fluoride-trifluoroethylene-chlorofloroethylene) terpolymer ferroelectric relaxor. The devices exhibit excellent performance including a large on/off ratio) and an insignificant leakage current. Moreover, the hysteresis characteristics are effectively modulated for its ferroelectric properties at low temperature. Additionally, a broad range photoresponse (visible to 1.55 µm) and a high sensitivity (>300 A/W, λ = 450 nm) are achieved. These results indicate that ferroelectric relaxor can be applied into the high-performance 2D optoelectronic devices.