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Results for “Biocomputational method”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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5 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Predicting transcription factor activity using prior biological information

Dysregulation of normal transcription factor activity is a common driver of disease. Therefore, the detection of aberrant transcription factor activity is important to understand disease pathogenesis. We have developed Priori, a method to predict transcription factor activity from RNA sequencing data. Priori has two key advantages over existing methods. First, Priori utilizes literature-supported regulatory information to identify transcription factor-target gene relationships. It then applies linear models to determine the impact of transcription factor regulation on the expression of its target genes. Second, results from a third-party benchmarking pipeline reveals that Priori detects aberrant activity from 124 single-gene perturbation experiments with higher sensitivity and specificity than 11 other methods. We applied Priori and other top-performing methods to predict transcription factor activity from two large primary patient datasets. Our work demonstrates that Priori uniquely discovered significant determinants of survival in breast cancer and identified mediators of drug response in leukemia.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1995

3-D Reconstruction of Macular Type II Cell Innervation Patterns in Space-Flight and Control Rats

A semiautomated method for reconstructing objects from serial thin sections has been developed in the Biocomputation Center. The method is being used to completely, for the first time, type II hair cells and their innervations. The purposes are to learn more about the fundamental circuitry of the macula on Earth and to determine whether changes in connectivities occur under space flight conditions. Data captured directly from a transmission electron microscope via a video camera are sent to a graphics workstation. There, the digitized micrographs are mosaicked into sections and contours are traced, registered and displayed by semiautomated methods. Current reconstructions are of type II cells from the medial part of rat maculas collected in-flight on the Space Life Sciences-2 mission, 4.5 hrs post-flight, and from a ground control. Results show that typical type II cells receive processes from tip to six nearby calyces or afferents. Nearly all processes are elongated and have bouton-like enlargements; some have numerous vesicles. Multiple (2 to 4) processes from a single calyx to a type II cell are common, and approximately 1/3 of the processes innervale 2 or 3 type II cells or a neighboring cluster. From 2% to 6% of the cells resemble type I cells morphologically but have demi-calyces. Thus far, increments in synaptic number in type II cells of flight rats are prominent along processes that supply two hair cells. It is clear that reconstruction methods provide insights into details of macular circuitry not obtainable by other techniques. The results demonstrate a morphological basis for interactions between adjacent receptive fields through feed back-feed forward connections, and for dynamic alterations in receptive field range and activity during preprocessing of linear acceleratory information by the maculas. The reconstruction method we have developed will find further applications in the study of the details of neuronal architecture of more complex systems, to seek out shared organizational properties or neuronal networks and to understand better localization of synaptic changes in altered environments.

Ross, Muriel Dorothy↗
NASA NTRS1994

Computational Approaches to Vestibular Research

The Biocomputation Center at NASA Ames Research Center is dedicated to a union between computational, experimental and theoretical approaches to the study of neuroscience and of life sciences in general. The current emphasis is on computer reconstruction and visualization of vestibular macular architecture in three-dimensions (3-D), and on mathematical modeling and computer simulation of neural activity in the functioning system. Our methods are being used to interpret the influence of spaceflight on mammalian vestibular maculas in a model system, that of the adult Sprague-Dawley rat. More than twenty 3-D reconstructions of type I and type II hair cells and their afferents have been completed by digitization of contours traced from serial sections photographed in a transmission electron microscope. This labor-intensive method has now been replace d by a semiautomated method developed in the Biocomputation Center in which conventional photography is eliminated. All viewing, storage and manipulation of original data is done using Silicon Graphics workstations. Recent improvements to the software include a new mesh generation method for connecting contours. This method will permit the investigator to describe any surface, regardless of complexity, including highly branched structures such as are routinely found in neurons. This same mesh can be used for 3-D, finite volume simulation of synapse activation and voltage spread on neuronal surfaces visualized via the reconstruction process. These simulations help the investigator interpret the relationship between neuroarchitecture and physiology, and are of assistance in determining which experiments will best test theoretical interpretations. Data are also used to develop abstract, 3-D models that dynamically display neuronal activity ongoing in the system. Finally, the same data can be used to visualize the neural tissue in a virtual environment. Our exhibit will depict capabilities of our computational approaches and some of our findings from their application. For example, our research has demonstrated that maculas of adult mammals retain the property of synaptic plasticity. Ribbon synapses increase numerically and undergo changes in type and distribution (p<0.0001) in type II hair cells after exposure to microgravity for as few as nine days. The finding of macular synaptic plasticity is pertinent to the clinic, and may help explain some. balance disorders in humans. The software used in our investigations will be demonstrated for those interested in applying it in their own research.

Ross, Muriel D.↗
NASA NTRS1996

3-D Imaging In Virtual Environment: A Scientific Clinical and Teaching Tool

The advent of powerful graphics workstations and computers has led to the advancement of scientific knowledge through three-dimensional (3-D) reconstruction and imaging of biological cells and tissues. The Biocomputation Center at NASA Ames Research Center pioneered the effort to produce an entirely computerized method for reconstruction of objects from serial sections studied in a transmission electron microscope (TEM). The software developed, ROSS (Reconstruction of Serial Sections), is now being distributed to users across the United States through Space Act Agreements. The software is in widely disparate fields such as geology, botany, biology and medicine. In the Biocomputation Center, ROSS serves as the basis for development of virtual environment technologies for scientific and medical use. This report will describe the Virtual Surgery Workstation Project that is ongoing with clinicians at Stanford University Medical Center, and the role of the Visible Human data in the project.

Ross, Muriel D.↗
NASA NTRS1995

Gravity Sensors and the Role of 3-D Visualization and Simulation in Biomedical Research

Ross 3.0 software was developed in the Biocomputation Center for semi-automated reconstruction of objects from serial thin sections. Data are captured directly from a transmission electron microscope via a video camera to a graphics workstation where the sections are mosaicked and contours are traced, registered and displayed by semi-automated methods. For the first time, macular type II cells are described completely for their innervation patterns. The purposes are to learn more about the fundamental circuitry of the macula and to demonstrate whether the terminals are altered morphologically by space flight. Current examples, from the medial part of the macula, are from maculas collected in-flight on the Space Life Sciences-2 mission, 4.5 hrs post-flight, and from a ground control. Results show that the typical type 11 cell receives processes from up to six nearby calyces or afferents. Nearly all the processes are elongated; some have bouton-like swellings and numerous vesicles. Multiple (2 to 4) processes from a single calyx to a type II cell are common, and approx. 1/3 of the processes innervate 2 type II cells of a neighboring cluster of 3 cells. About 2% of type II cells resemble type I cells morphologically and are surrounded by demicalyces. Differences in size or shape of the terminals under flight conditions could not be determined because the sample size is still too small; but it is clear that reconstruction methods provide insights into macular circuitry not obtainable by other techniques. The results demonstrate a morphological basis for interactions between adjacent receptive fields, through feedback-feedforward connections, during preprocessing of linear acceleratory information by the maculas. While the methods are currently being tested using vestibular maculas as the model system, it is clear that the technology is applicable to any tissue that can be physically or optically sectioned. ROSS software has already been implemented for reconstructing objects from tissues studied by confocal and by transmitted light microscopy, and research into magnetic resonance imaging-computational tomography combined visualization are underway.

Ross, Muriel D.↗