scholarly journals Constructing and Visualizing Cancer Genomic Maps in 3D Spatial Context by Phenotype-based High-throughput Laser-aided Isolation and Sequencing (PHLI-seq)

2018 ◽  
Author(s):  
Sungsik Kim ◽  
Amos Chungwon Lee ◽  
Han-Byoel Lee ◽  
Jinhyun Kim ◽  
Yushin Jung ◽  
...  

A spatially resolved analysis of the heterogeneous cancer genome, in which the data are connected to the three-dimensional space of a tumour, is crucial to understand cancer biology and the clinical impact of cancer heterogeneity on patients. However, despite recent progress in spatially resolved transcriptomics, spatial mapping of genomic data in a high-throughput and high-resolution manner has been challenging due to current technical limitations. Here, we describe a novel approach, phenotype-based high-throughput laser-aided isolation and sequencing (PHLI-seq), which enables high-throughput isolation of a single-cell or a small number of cells and their genome-wide sequence analysis to construct genomic maps within cancer tissue in relation to the phenotypes of the cells. By applying PHLI-seq, we reveal the heterogeneity of breast cancer tissues at a high resolution and map the genomic landscape of the cells to their corresponding spatial locations and phenotypes in the tumour mass. Additionally, with different staining modalities, the genotypes of the cells can be connected to corresponding phenotypic information of the tissue. Together with the spatially resolved genomic analysis, we can infer the histories of heterogeneous cancer cells in two or three dimensions, providing significant insight into cancer biology and precision medicine.

2021 ◽  
Author(s):  
Dario Bressan ◽  
Claire M Mulvey ◽  
Fatime Qosaj ◽  
Robert Becker ◽  
Flaminia Grimaldi ◽  
...  

A set of increasingly powerful approaches are enabling spatially resolved measurements of growing numbers of molecular features in biological samples. While important insights can be derived from the two-dimensional data that many of these technologies generate, it is clear that extending these approaches into the third and fourth dimensions will magnify their impact. Realizing biological insights from datasets where thousands to millions of cells are annotated with tens to hundreds of parameters in space will require the development of new computational and visualization strategies. Here, we describe Theia, a virtual reality-based platform, which enables exploration and analysis of either volumetric or segmented, molecularly-annotated, three-dimensional datasets, with the option to extend the analysis to time-series data. We also describe our pipeline for generating annotated 3D models of breast cancer and supply several datasets to enable users to explore the utility of Theia for understanding cancer biology in three dimensions.


1997 ◽  
Vol 84 (1) ◽  
pp. 176-178
Author(s):  
Frank O'Brien

The author's population density index ( PDI) model is extended to three-dimensional distributions. A derived formula is presented that allows for the calculation of the lower and upper bounds of density in three-dimensional space for any finite lattice.


1989 ◽  
Vol 94 (4) ◽  
pp. 617-624
Author(s):  
S.J. Wright ◽  
J.S. Walker ◽  
H. Schatten ◽  
C. Simerly ◽  
J.J. McCarthy ◽  
...  

Applications of the tandem scanning confocal microscope (TSM) to fluorescence microscopy and its ability to resolve fluorescent biological structures are described. The TSM, in conjunction with a cooled charge-coupled device (cooled CCD) and conventional epifluorescence light source and filter sets, provided high-resolution, confocal data, so that different fluorescent cellular components were distinguished in three dimensions within the same cell. One of the unique features of the TSM is the ability to image fluorochromes excited by ultraviolet light (e.g. Hoechst, DAPI) in addition to fluorescein and rhodamine. Since the illumination is dim, photobleaching is insignificant and prolonged viewing of living specimens is possible. Series of optical sections taken in the Z-axis with the TSM were reproduced as stereo images and three-dimensional reconstructions. These data show that the TSM is potentially a powerful tool in fluorescence microscopy for determining three-dimensional relationships of complex structures within cells labeled with multiple fluorochromes.


2008 ◽  
Vol 99 (5) ◽  
pp. 2602-2616 ◽  
Author(s):  
Marion R. Van Horn ◽  
Pierre A. Sylvestre ◽  
Kathleen E. Cullen

When we look between objects located at different depths the horizontal movement of each eye is different from that of the other, yet temporally synchronized. Traditionally, a vergence-specific neuronal subsystem, independent from other oculomotor subsystems, has been thought to generate all eye movements in depth. However, recent studies have challenged this view by unmasking interactions between vergence and saccadic eye movements during disconjugate saccades. Here, we combined experimental and modeling approaches to address whether the premotor command to generate disconjugate saccades originates exclusively in “vergence centers.” We found that the brain stem burst generator, which is commonly assumed to drive only the conjugate component of eye movements, carries substantial vergence-related information during disconjugate saccades. Notably, facilitated vergence velocities during disconjugate saccades were synchronized with the burst onset of excitatory and inhibitory brain stem saccadic burst neurons (SBNs). Furthermore, the time-varying discharge properties of the majority of SBNs (>70%) preferentially encoded the dynamics of an individual eye during disconjugate saccades. When these experimental results were implemented into a computer-based simulation, to further evaluate the contribution of the saccadic burst generator in generating disconjugate saccades, we found that it carries all the vergence drive that is necessary to shape the activity of the abducens motoneurons to which it projects. Taken together, our results provide evidence that the premotor commands from the brain stem saccadic circuitry, to the target motoneurons, are sufficient to ensure the accurate control shifts of gaze in three dimensions.


1998 ◽  
Vol 4 (S2) ◽  
pp. 16-17
Author(s):  
David Scharf ◽  
Jacob Wilbrink ◽  
John A. Hunt

A stop-frame animation system has been developed for producing high-resolution, color and stereo motion picture animation sequences. The first of these sequences can be seen in the recently released IMAX 3D movies, “Four Million House Guests” a.k.a. “The Hidden Dimension”. IMAX movies have long been known for their breathtaking special effects that seem incredibly realistic because of the large projection screen (about 7 stories high) which is close to the entire audience, high resolution, and powerful audio effects. IMAX 3D is an extention to the traditional format that allows the audience to see three dimensional special effects with the aid of electronically shuttered viewing glasses. IMAX movies are an ideal medium to demonstrate the high resolution digital images that are possible with the SEM.The goal of the SEM movie project was to produce movie sequences where viewers feels like they are flying smoothly through micro-space past microscopic creatures and objects in three dimensions and in color.


2019 ◽  
Vol 3 (1) ◽  
pp. 223-234 ◽  
Author(s):  
Hans Clevers ◽  
David A. Tuveson

Organoid cultures have emerged as powerful model systems accelerating discoveries in cellular and cancer biology. These three-dimensional cultures are amenable to diverse techniques, including high-throughput genome and transcriptome sequencing, as well as genetic and biochemical perturbation, making these models well suited to answer a variety of questions. Recently, organoids have been generated from diverse human cancers, including breast, colon, pancreas, prostate, bladder, and liver cancers, and studies involving these models are expanding our knowledge of the etiology and characteristics of these malignancies. Co-cultures of cancer organoids with non-neoplastic stromal cells enable investigation of the tumor microenvironment. In addition, recent studies have established that organoids have a place in personalized medicine approaches. Here, we describe the application of organoid technology to cancer discovery and treatment.


2019 ◽  
Vol 11 (2) ◽  
pp. 131 ◽  
Author(s):  
Lu An ◽  
Eric Rignot ◽  
Romain Millan ◽  
Kirsty Tinto ◽  
Josh Willis

Marine-terminating glaciers dominate the evolution of the Greenland Ice Sheet (GrIS) and its contribution to sea-level rise. Widespread glacier acceleration has been linked to the warming of ocean waters around the periphery of Greenland but a lack of information on the bathymetry of the continental shelf and glacial fjords has limited our ability to understand how subsurface, warm, salty ocean waters of Atlantic origin (AW) reach the glaciers and melt them from below. Here, we employ high-resolution, airborne gravity data (AIRGrav) in combination with multibeam echo sounding (MBES) data, to infer the bathymetry of the coastal areas of Northwest Greenland for NASA’s Ocean Melting Greenland (OMG) mission. High-resolution, AIRGrav data acquired on a 2 km spacing, 150 m ground clearance, with 1.5 mGal crossover error, is inverted in three dimensions to map the bathymetry. To constrain the inversion away from MBES data, we compare two methods: one based on the Direct Current (DC) shift of the gravity field (absolute minus observed gravity) and another based on the density of the bedrock. We evaluate and compare the two methods in areas with complete MBES coverage. We find the lowest standard error in bed elevation (±60 m) using the DC shift method. When applied to the entire coast of Northwest Greenland, the three-dimensional inversion reveals a complex network of connected sea bed channels, not known previously, that provide natural and varied pathways for AW to reach the glaciers across the continental shelf. The study demonstrates that the gravity approach offers an efficient and practical alternative to extensive ship mapping in ice-filled waters to obtain information critical to understanding and modeling ice-ocean interaction along ice sheet margins.


2020 ◽  
Vol 9 (11) ◽  
pp. 620
Author(s):  
Xiran Zhou ◽  
Xiao Xie ◽  
Yong Xue ◽  
Bing Xue ◽  
Kai Qin ◽  
...  

High-resolution digital elevation models (DEMs) and its derivatives (e.g., curvature, slope, aspect) offer a great possibility of representing the details of Earth’s surface in three-dimensional space. Previous research investigations concerning geomorphological variables and region-level features alone cannot precisely characterize the main structure of landforms. However, these geomorphological variables are not sufficient to represent a complex landform object’s whole structure from a high-resolution DEM. Moreover, the amount of the DEM dataset is limited, including the landform object. Considering the challenges above, this paper reports an integrated model called the bag of geomorphological words (BoGW), enabling automatic landform recognition via integrating point and linear geomorphological variables, region-based features (e.g., shape, texture), and high-level landform descriptions. First, BoGW semantically characterizes the composition of geomorphological variables and meaningful parcels of each type of landform. Based on a landform’s semantics, the proposed method then integrates geomorphological variables and region-level features (e.g., shape, texture) to create the feature vector for the landform. Finally, BoGW classifies a region derived from high-resolution DEM into a predefined type of landform by the feature vector. The experimental results on crater and cirque detection indicated that the proposed BoGW could support landform object recognition from high-resolution DEMs.


1993 ◽  
Vol 2 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Kristinn R. Thorisson

The most common visual feedback technique in teleoperation is in the form of monoscopic video displays. As robotic autonomy increases and the human operator takes on the role of a supervisor, three-dimensional information is effectively presented by multiple, televised, two-dimensional (2-D) projections showing the same scene from different angles. To analyze how people go about using such segmented information for estimations about three-dimensional (3-D) space, 18 subjects were asked to determine the position of a stationary pointer in space; eye movements and reaction times (RTs) were recorded during a period when either two or three 2-D views were presented simultaneously, each showing the same scene from a different angle. The results revealed that subjects estimated 3-D space by using a simple algorithm of feature search. Eye movement analysis supported the conclusion that people can efficiently use multiple 2-D projections to make estimations about 3-D space without reconstructing the scene mentally in three dimensions. The major limiting factor on RT in such situations is the subjects' visual search performance, giving in this experiment a mean of 2270 msec (SD = 468; N = 18). This conclusion was supported by predictions of the Model Human Processor (Card, Moran, & Newell, 1983), which predicted a mean RT of 1820 msec given the general eye movement patterns observed. Single-subject analysis of the experimental data suggested further that in some cases people may base their judgments on a more elaborate 3-D mental model reconstructed from the available 2-D views. In such situations, RTs and visual search patterns closely resemble those found in the mental rotation paradigm (Just & Carpenter, 1976), giving RTs in the range of 5-10 sec.


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