skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: OrgDyn: feature- and model-based characterization of spatial and temporal organoid dynamics
Abstract Summary Organoid model systems recapitulate key features of mammalian tissues and enable high throughput experiments. However, the impact of these experiments may be limited by manual, non-standardized, static or qualitative phenotypic analysis. OrgDyn is an open-source and modular pipeline to quantify organoid shape dynamics using a combination of feature- and model-based approaches on time series of 2D organoid contour images. Our pipeline consists of (i) geometrical and signal processing feature extraction, (ii) dimensionality reduction to differentiate dynamical paths, (iii) time series clustering to identify coherent groups of organoids and (iv) dynamical modeling using point distribution models to explain temporal shape variation. OrgDyn can characterize, cluster and model differences among unique dynamical paths that define diverse final shapes, thus enabling quantitative analysis of the molecular basis of tissue development and disease. Availability and Implementation https://github.com/zakih/organoidDynamics (BSD 3-Clause License). Supplementary information Supplementary data are available at Bioinformatics online.  more » « less
Award ID(s):
1720625
PAR ID:
10188165
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ;
Date Published:
Journal Name:
Bioinformatics
Volume:
36
Issue:
10
ISSN:
1367-4803
Page Range / eLocation ID:
3292 to 3294
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. This paper presents a generative statistical model for analyzing time series of planar shapes. Using elastic shape analysis, we separate object kinematics (rigid motions and speed variability) from morphological evolution, representing the latter through transported velocity fields (TVFs). A principal component analysis (PCA) based dimensionality reduction of the TVF representation provides a finite-dimensional Euclidean framework, enabling traditional time-series analysis. We then fit a vector auto-regressive (VAR) model to the TVF-PCA time series, capturing the statistical dynamics of shape evolution. To characterize morphological changes,we use VAR model parameters for model comparison, synthesis, and sequence classification. Leveraging these parameters, along with machine learning classifiers, we achieve high classification accuracy. Extensive experiments on cell motility data validate our approach, demonstrating its effectiveness in modeling and classifying migrating cells based on morphological evolution—marking a novel contribution to the field. 
    more » « less
  2. Detection and attribution (DA) studies are cornerstones of climate science, providing crucial evidence for policy decisions. Their goal is to link observed climate change patterns to anthropogenic and natural drivers via the optimal fingerprinting method (OFM). We show that response theory for nonequilibrium systems offers the physical and dynamical basis for OFM, including the concept of causality used for attribution. Our framework clarifies the method’s assumptions, advantages, and potential weaknesses. We use our theory to perform DA for prototypical climate change experiments performed on an energy balance model and on a low-resolution coupled climate model. We also explain the underpinnings of degenerate fingerprinting, which offers early warning indicators for tipping points. Finally, we extend the OFM to the nonlinear response regime. Our analysis shows that OFM has broad applicability across diverse stochastic systems influenced by time-dependent forcings, with potential relevance to ecosystems, quantitative social sciences, and finance, among others. Published by the American Physical Society2024 
    more » « less
  3. Traditionally, tissue-specific organoids are generated as 3D aggregates of stem cells embedded in Matrigel or hydrogels, and the aggregates eventually end up a spherical shape and suspended in the matrix. Lack of geometrical control of organoid formation makes these spherical organoids limited for modeling the tissues with complex shapes. To address this challenge, we developed a new method to generate 3D spatial-organized cardiac organoids from 2D micropatterned human induced pluripotent stem cell (hiPSC) colonies, instead of directly from 3D stem cell aggregates. This new approach opens the possibility to create cardiac organoids that are templated by 2D non-spherical geometries, which potentially provides us a deeper understanding of biophysical controls on developmental organogenesis. Here, we designed 2D geometrical templates with quadrilateral shapes and pentagram shapes that had same total area but different geometrical shapes. Using this templated substrate, we grew cardiac organoids from hiPSCs and collected a series of parameters to characterize morphological and functional properties of the cardiac organoids. In quadrilateral templates, we found that increasing the aspect ratio impaired cardiac tissue 3D self-assembly, but the elongated geometry improved the cardiac contractile functions. However, in pentagram templates, cardiac organoid structure and function were optimized with a specific geometry of an ideal star shape. This study will shed a light on “organogenesis-by-design” by increasing the intricacy of starting templates from external geometrical cues to improve the organoid morphogenesis and functionality. 
    more » « less
  4. Recent channel state information (CSI)-based positioning pipelines rely on deep neural networks (DNNs) in order to learn a mapping from estimated CSI to position. Since real-world communication transceivers suffer from hardware impairments, CSI-based positioning systems typically rely on features that are designed by hand. In this paper, we propose a CSI-based positioning pipeline that directly takes raw CSI measurements and learns features using a structured DNN in order to generate probability maps describing the likelihood of the transmitter being at pre-defined grid points. To further improve the positioning accuracy of moving user equipments, we propose to fuse a time-series of learned CSI features or a time-series of probability maps. To demonstrate the efficacy of our methods, we perform experiments with real-world indoor line-of-sight (LoS) and nonLoS channel measurements. We show that CSI feature learning and time-series fusion can reduce the mean distance error by up to 2.5× compared to the state-of-the-art. 
    more » « less
  5. Abstract Cardiac organoids have emerged as powerful platforms for modeling human heart development and disease. However, traditional 2D microelectrode arrays (MEAs) are limited to planar recordings and fail to capture the 3D propagation of electrical signals. Here, programmable, shape‐adaptive, organoid‐encapsulating shell MEAs are presented as a technology that enables comprehensive 3D electrophysiological mapping. These on‐chip‐fabricated devices feature customizable geometries and electrode layouts tailored to an organoid's unique morphology. Shell MEAs generate high‐resolution 3D isochrone and conduction velocity maps, unveiling long‐term spatiotemporal field potential dynamics in spontaneously beating organoids. Furthermore, they integrate multiple modalities, such as calcium imaging to corroborate electrophysiological findings and pharmacological screening to assess organoid responses to isoproterenol, E‐4031, and serotonin. This platform represents a significant advance in bioelectronic interfaces, enabling high‐content 3D spatiotemporal functional analysis for cardiac disease modeling and pharmacological testing. 
    more » « less