Dataset Information

Modeling transcriptomic age using knowledge-primed artificial neural networks.

ABSTRACT: The development of 'age clocks', machine learning models predicting age from biological data, has been a major milestone in the search for reliable markers of biological age and has since become an invaluable tool in aging research. However, beyond their unquestionable utility, current clocks offer little insight into the molecular biological processes driving aging, and their inner workings often remain non-transparent. Here we propose a new type of age clock, one that couples predictivity with interpretability of the underlying biology, achieved through the incorporation of prior knowledge into the model design. The clock, an artificial neural network constructed according to well-described biological pathways, allows the prediction of age from gene expression data of skin tissue with high accuracy, while at the same time capturing and revealing aging states of the pathways driving the prediction. The model recapitulates known associations of aging gene knockdowns in simulation experiments and demonstrates its utility in deciphering the main pathways by which accelerated aging conditions such as Hutchinson-Gilford progeria syndrome, as well as pro-longevity interventions like caloric restriction, exert their effects.

SUBMITTER: Holzscheck N

PROVIDER: S-EPMC8169742 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Modeling transcriptomic age using knowledge-primed artificial neural networks.

Holzscheck Nicholas N Falckenhayn Cassandra C Söhle Jörn J Kristof Boris B Siegner Ralf R Werner André A Schössow Janka J Jürgens Clemens C Völzke Henry H Wenck Horst H Winnefeld Marc M Grönniger Elke E Kaderali Lars L

NPJ aging and mechanisms of disease 20210601 1

The development of 'age clocks', machine learning models predicting age from biological data, has been a major milestone in the search for reliable markers of biological age and has since become an invaluable tool in aging research. However, beyond their unquestionable utility, current clocks offer little insight into the molecular biological processes driving aging, and their inner workings often remain non-transparent. Here we propose a new type of age clock, one that couples predictivity with ...[more]

PMID: 34075044

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Project description:The imperative to decarbonize the energy sector has prompted substantial advancements in clean electricity generation, with hydrogen emerging as a promising low-carbon energy carrier. While hydrogen synthesis from renewable sources is crucial, challenges persist, necessitating innovative approaches for efficient and sustainable production. This study leverages diverse artificial neural network (ANN) models to assess and predict system efficiency based on key operational variables in membrane reactor systems. The multilayered perceptron (MLP) and radial basis function (RBF) methodologies are employed, with the MLP models optimized across twelve training algorithms and eight activation functions, exploring up to three hidden layers with variable neuron counts. The MLP model, utilizing the Levenberg-Marquard training algorithm and Tangent-Sigmoid activation function, achieved a high correlation coefficient (R2) of 0.9975 for training and 0.9962 for testing, and a mean squared error (MSE) of 0.00425 for training and 0.23951 for testing, indicating precise and accurate efficiency predictions. The Log-Sigmoid activation function also performed well, with R² values of 0.9971 (training) and 0.9961 (testing), and MSE values of 0.004086 (training) and 0.17694 (testing). Optimization of the RBF network identified the best performance with a spread parameter of 1 and 35 neurons, although the MLP model demonstrated superior accuracy and reduced computational time. Statistical analysis, encompassing correlation coefficient, mean squared error, Root Mean Squared error, absolute average deviation, absolute average relative deviation, and runtime, confirms the network's consistent and accurate estimation of system efficiency across various input variables. The study highlights that applying tansig and logsig activation functions, configured with neuron counts of 20, 17, 6 and 23, 20, 2 at the first, second and third hidden layers, respectively, offers enhanced accuracy and reliability. The MLP model's high performance underscores its potential to identify optimal conditions for H2 generation based on system efficiency, thereby advancing membrane reactor technology for hydrogen production.

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Project description:Over the last decade, numerous computational methods have been developed in order to infer and model biological networks. Transcriptional networks in particular have attracted significant attention due to their critical role in cell survival. The majority of network inference methods use genome-wide experimental data to search for modules of genes with coherent expression profiles and common regulators, often ignoring the multi-layer structure of transcriptional cascades. Modeling methodologies on the other hand assume a given network structure and vary significantly in their algorithmic approach, ranging from over-simplified representations (e.g., Boolean networks) to detailed -but computationally expensive-network simulations (e.g., with differential equations). In this work we use Artificial Neural Networks (ANNs) to model transcriptional regulatory cascades that emerge during the stress response in Saccharomyces cerevisiae and extend in three layers. We confine the structure of the ANNs to match the structure of the biological networks as determined by gene expression, DNA-protein interaction and experimental evidence provided in publicly available databases. Trained ANNs are able to predict the expression profile of 11 target genes across multiple experimental conditions with a correlation coefficient >0.7. When time-dependent interactions between upstream transcription factors (TFs) and their indirect targets are also included in the ANNs, accurate predictions are achieved for 30/34 target genes. Moreover, heterodimer formation is taken into account. We show that ANNs can be used to (1) accurately predict the expression of downstream genes in a 3-layer transcriptional cascade based on the expression of their indirect regulators and (2) infer the condition- and time-dependent activity of various TFs as well as during heterodimer formation. We show that a three-layer regulatory cascade whose structure is determined by co-expressed gene modules and their regulators can successfully be modeled using ANNs with a similar configuration.

Dataset Information

Modeling transcriptomic age using knowledge-primed artificial neural networks.

Publications

Modeling transcriptomic age using knowledge-primed artificial neural networks.

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