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Tsutsumi, S.

Publications and source records attributed to Tsutsumi, S..

7 recordsLinked to original sources

Multi-objective computational optimization of human 5' UTR sequences

The computational design of mRNA sequences is a critical technology for both scientific research and industrial applications. Recent advances in prediction and optimization models have enabled the automatic scoring and optimization of 5' UTR sequences, key upstream elements of mRNA. However, fully automated design of 5' UTR sequences with more than two objective scores has not yet been explored. In this study, we present a computational pipeline that optimizes human 5' UTR sequences in a multi-objective framework, addressing up to four distinct and conflicting objectives. Our work represents an important advancement in the multi-objective computational design of mRNA sequences, paving the way for more sophisticated mRNA engineering.

bioinformatics↗

JG2: an updated version of the Japanese population-specific reference genome

This study presents the construction of JG2, an updated population-specific reference genome for the Japanese population. Utilizing data from three individuals previously employed in the construction of JG1, several methodologies were employed to enhance genomic coverage and assembly quality. Hi-C sequencing technology facilitated phase-aware assembly, generating two haploid assemblies per individual and enabling improved representation of genetic variation. A meta-assembly strategy and a majority decision approach further refined assembly quality by combining the best sequences from multiple assemblies and minimizing the inclusion of rare variants. The resulting JG2 genome comprises chromosome-level sequences, mitochondrial chromosomes, and unplaced scaffolds, offering more comprehensive coverage of the Japanese genome. Comparative analyses with other reference genomes demonstrated the accuracy and representativeness of JG2, highlighting its utility for genetic research involving the Japanese population. Overall, by adopting the phased assembly technique, JG2 represents a significant advancement over the collapsed assembly-based JG1, providing researchers with a more precise and comprehensive resource for understanding the genetic landscape of the Japanese population. The sequences and annotations are available on the jMorp website (https://jmorp.megabank.tohoku.ac.jp/).

genomics↗

Negative reward-prediction errors of climbing fiber inputs for cerebellar reinforcement learning algorithm

Although the cerebellum is typically linked to supervised learning algorithms, it also exhibits extensive involvement in reward processing. In this study, we investigated the cerebellums role in executing reinforcement learning algorithms, with a particular emphasis on essential reward-prediction errors. We employed the Q-learning model to accurately reproduce the licking responses of mice in a Go/No-go auditory-discrimination task. This method enabled the calculation of reinforcement learning variables, such as reward, predicted reward, and reward-prediction errors in each learning trial. By tensor component analysis of two-photon Ca2+ imaging data from more than 6,000 Purkinje cells, we found that climbing fiber inputs of the two distinct components, which were specifically activated during Go and No-go cues in the learning process, showed an inverse relationship with predictive reward-prediction errors. By assuming bidirectional parallel-fiber Purkinje-cell synaptic plasticity, we constructed a cerebellar neural-network model with 5,000 spiking neurons of granule cells, Purkinje cells, cerebellar nuclei neurons, and inferior olive neurons. The network model qualitatively reproduced distinct changes in licking behaviors, climbing-fiber firing rates and their synchronization during discrimination learning separately for Go/No-go conditions. We found that Purkinje cells in the two components could develop specific motor commands for their respective auditory cues, guided by the predictive reward-prediction errors from their climbing fiber inputs. These results indicate a possible role of context-specific actors in modular reinforcement learning, integrating with cerebellar supervised learning capabilities.

neuroscience↗

Dynamic organization of cerebellar climbing fiber response and synchrony in multiple functional modules reduces dimensions for reinforcement learning

Daynamic functional organization by synchronization is theorized to be essential for dimension reduction of the cerebellar learning space. We analyzed a large amount of coordinate-localized, two-photon imaging data from cerebellar Crus II in mice undergoing "Go/No-go" reinforcement learning. Tensor component analysis revealed that a majority of climbing fiber inputs to Purkinje cells were reduced to only four functional components, corresponding to accurate timing control of motor initiation related to a Go cue, cognitive error-based learning, reward processing, and inhibition of erroneous behaviors after a No-go cue. Spatial distribution of these components coincided well with the boundaries of Aldolase-C/zebrin II expression in Purkinje cells, whereas several components are mixed in single neurons. Synchronization within individual components was bidirectionally regulated according to specific task contexts and learning stages. These findings suggest that the cerebellum, based on anatomical compartments, reduces dimensions by self-organization of components, a feature that may inspire new-generation AI designs.

neuroscience↗

Cerebellar climbing fibers convey behavioral information of multiplex modalities and form functional modules

Cerebellar climbing fibers (CFs) convey sensorimotor information and their errors, which are used for motor control and learning. Furthermore, they represent reward-related information. Despite such functional diversity of CF signals, it is still unclear whether each CF conveys the information of single or multiple modalities and how the CFs conveying different information are distributed over the cerebellar cortex. We performed two-photon calcium imaging from cerebellar Purkinje cells (PCs) in mice engaged in a voluntary forelimb lever-pull task and demonstrated that CF responses in 93% of PCs could be explained by the combination of multiple behavioral variables, such as lever movement, licking, and reward delivery. Neighboring PCs exhibited similar CF response properties, formed functional clusters, and shared noise fluctuations of responses. Taken together, individual CFs convey behavioral information on multiplex variables and are spatially organized into the functional modules of the cerebellar cortex.

neuroscience↗

Precise hyperacuity estimation of spike timing from calcium imaging

Two-photon imaging is a major recording technique in neuroscience, but it suffers from several limitations, including a low sampling rate, the nonlinearity of calcium responses, the slow dynamics of calcium dyes and a low signal-to-noise ratio, all of which impose a severe limitation on the application of two-photon imaging in elucidating neuronal dynamics with high temporal resolution. Here, we developed a hyperacuity algorithm (HA_time) based on an approach combining a generative model and machine learning to improve spike detection and the precision of spike time inference. First, Bayesian inference estimates the calcium spike model by assuming the constancy of the spike shape and size. A support vector machine employs this information and detects spikes with higher temporal precision than the sampling rate. Compared with conventional thresholding, HA_time improved the precision of spike time estimation up to 20-fold for simulated calcium data. Furthermore, the benchmark analysis of experimental data from different brain regions and simulation of a broader range of experimental conditions showed that our algorithm was among the best in a class of hyperacuity algorithms. We encourage experimenters to use the proposed algorithm to precisely estimate hyperacuity spike times from two-photon imaging.

neuroscience↗

Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells

BackgroundEndothelial cells (ECs) make up the innermost layer throughout the entire vasculature. Their phenotypes and physiological functions are initially regulated by developmental signals and extracellular stimuli. The underlying molecular mechanisms responsible for the diverse phenotypes of ECs from different organs are not well understood.\n\nResultsTo characterize the transcriptomic and epigenomic landscape in the vascular system, we cataloged gene expression and active histone marks in nine types of human ECs (generating 148 genome-wide datasets) and carried out a comprehensive analysis with chromatin interaction data. We identified 3,765 EC-specific enhancers, some of which were associated with disease-associated genetic variations. We also identified various candidate marker genes for each EC type. Notably, reflecting the developmental origins of ECs and their roles in angiogenesis, vasculogenesis and wound healing.\n\nConclusionsWhile the importance of several HOX genes for early vascular development and adult angiogenesis in pathological conditions has been reported, a systematic analysis of the regulation and roles of HOX genes in mature tissue cells has been lacking. These datasets provide a valuable resource for understanding the vascular system and associated diseases.

genomics↗