Shahbaba, B. | Search bioRxiv

bioRxiv2023

tauFisher accurately predicts circadian time from a single sample of bulk and single-cell transcriptomic data

As the circadian clock regulates fundamental biological processes, disrupted clocks are often observed in patients and diseased tissues. Determining the circadian time of the patient or the tissue of focus is essential in circadian medicine and research. Here we present tau-Fisher, a computational pipeline that accurately predicts circadian time from a single transcriptomic sample by finding correlations between rhythmic genes within the sample. We demonstrate tauFishers out-standing performance in both bulk and single-cell transcriptomic data collected from multiple tissue types and experimental settings. Application of tauFisher at a cell-type level in a single-cell RNA-seq dataset collected from mouse dermal skin implies that greater circadian phase heterogeneity may explain the dampened rhythm of collective core clock gene expression in dermal immune cells compared to dermal fibroblasts. Given its robustness and generalizability across assay platforms, experimental setups, and tissue types, as well as its potential application in single-cell RNA-seq data analysis, tauFisher is a promising tool that facilitates circadian medicine and research.

bioinformatics↗

bioRxiv2019

Hippocampal ensembles represent sequential relationships among discrete nonspatial events

The hippocampus is critical to the temporal organization of our experiences, including the ability to remember past event sequences and predict future ones. Although this fundamental capacity is conserved across modalities and species, its underlying neuronal mechanisms remain poorly understood. Here we recorded hippocampal ensemble activity as rats remembered a sequence of nonspatial events (5 odor presentations unfolding over several seconds), using a task with established parallels in humans. Using novel statistical methods and deep learning techniques, we then identified new forms of sequential organization in hippocampal activity linked with task performance. We discovered that sequential firing fields ("time cells") provided temporal information within and across events in the sequence, and that distinct types of task-critical information (stimulus identity, temporal order, and trial outcome) were also sequentially differentiated within event presentations. Finally, as previously only observed with spatial information, we report that the representations of past, present and future events were sequentially activated within individual event presentations, and that these sequential representations could be compressed within an individual theta cycle. These findings strongly suggest that a fundamental function of the hippocampal network is to encode and preserve the sequential order of experiences, and use these representations to generate predictions to inform decision-making.

neuroscience↗