Synaptic receptors in the human brain consist of multiple protein subunits, many of which have multiple variants, coded by different genes, and are differentially expressed across brain regions and developmental stages. The brain can tune the electrophysiological properties of synapses to regulate plasticity and information processing by switching from one protein variant to another. Such condition-dependent variant switch during development has been demonstrated in several neurotransmitter systems including NMDA and GABA. Here we systematically detect pairs of receptor-subunit variants that switch during the lifetime of the human brain by analyzing postmortem expression data collected in a population of donors at various ages and brain regions measured using microarray and RNA-seq. To further detect variant pairs that co-vary across subjects, we present a method to quantify age-corrected expression correlation in face of strong temporal trends. This is achieved by computing the correlations in the residual expression beyond a cubic-spline model of the population temporal trend, and can be seen as a nonlinear version of partial correlations. Using these methods, we detect multiple new pairs of context dependent variants. For instance, we find a switch from GLRA2 to GLRA3 that differs from the known switch in the rat. We also detect an early switch from HTR1A to HTR5A whose trends are negatively correlated and find that their age-corrected expression is strongly positively correlated. Finally, we observe that GRIN2B switch to GRIN2A occurs mostly during embryonic development, presumably earlier than observed in rodents. These results provide a systematic map of developmental switching in the neurotransmitter systems of the human brain.
Abstract. Google's operational flood forecasting system was developed to provide accurate real-time flood warnings to agencies and the public with a focus on riverine floods in large, gauged rivers. It became operational in 2018 and has since expanded geographically. This forecasting system consists of four subsystems: data validation, stage forecasting, inundation modeling, and alert distribution. Machine learning is used for two of the subsystems. Stage forecasting is modeled with the long short-term memory (LSTM) networks and the linear models. Flood inundation is computed with the thresholding and the manifold models, where the former computes inundation extent and the latter computes both inundation extent and depth. The manifold model, presented here for the first time, provides a machine-learning alternative to hydraulic modeling of flood inundation. When evaluated on historical data, all models achieve sufficiently high-performance metrics for operational use. The LSTM showed higher skills than the linear model, while the thresholding and manifold models achieved similar performance metrics for modeling inundation extent. During the 2021 monsoon season, the flood warning system was operational in India and Bangladesh, covering flood-prone regions around rivers with a total area close to 470 000 km2, home to more than 350 000 000 people. More than 100 000 000 flood alerts were sent to affected populations, to relevant authorities, and to emergency organizations. Current and future work on the system includes extending coverage to additional flood-prone locations and improving modeling capabilities and accuracy.
Abstract. Google’s operational flood forecasting system was developed to provide accurate real-time flood warnings to agencies and the public, with a focus on riverine floods in large, gauged rivers. It became operational in 2018 and has since expanded geographically. This forecasting system consists of four subsystems: data validation, stage forecasting, inundation modeling, and alert distribution. Machine learning is used for two of the subsystems. Stage forecasting is modeled with the Long Short-Term Memory (LSTM) networks and the Linear models. Flood inundation is computed with the Thresholding and the Manifold models, where the former computes inundation extent and the latter computes both inundation extent and depth. The Manifold model, presented here for the first time, provides a machine-learning alternative to hydraulic modeling of flood inundation. When evaluated on historical data, all models achieve sufficiently high-performance metrics for operational use. The LSTM showed higher skills than the Linear model, while the Thresholding and Manifold models achieved similar performance metrics for modeling inundation extent. During the 2021 monsoon season, the flood warning system was operational in India and Bangladesh, covering flood-prone regions around rivers with a total area of 287,000 km2, home to more than 350M people. More than 100M flood alerts were sent to affected populations, to relevant authorities, and to emergency organizations. Current and future work on the system includes extending coverage to additional flood-prone locations, as well as improving modeling capabilities and accuracy.
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