scholarly journals ClonArch: visualizing the spatial clonal architecture of tumors

2020 ◽  
Vol 36 (Supplement_1) ◽  
pp. i161-i168
Author(s):  
Jiaqi Wu ◽  
Mohammed El-Kebir
Keyword(s):  
Visual Analytics ◽  
Phylogenetic Trees ◽  
Cancer Genomics ◽  
Clonal Evolution ◽  
Response To Treatment ◽  
Tumor Evolution ◽  
Web Based ◽  
Clonal Architecture ◽  
Spatial Coordinates ◽  
Carcinoma Tumor

Abstract Motivation Cancer is caused by the accumulation of somatic mutations that lead to the formation of distinct populations of cells, called clones. The resulting clonal architecture is the main cause of relapse and resistance to treatment. With decreasing costs in DNA sequencing technology, rich cancer genomics datasets with many spatial sequencing samples are becoming increasingly available, enabling the inference of high-resolution tumor clones and prevalences across different spatial coordinates. While temporal and phylogenetic aspects of tumor evolution, such as clonal evolution over time and clonal response to treatment, are commonly visualized in various clonal evolution diagrams, visual analytics methods that reveal the spatial clonal architecture are missing. Results This article introduces ClonArch, a web-based tool to interactively visualize the phylogenetic tree and spatial distribution of clones in a single tumor mass. ClonArch uses the marching squares algorithm to draw closed boundaries representing the presence of clones in a real or simulated tumor. ClonArch enables researchers to examine the spatial clonal architecture of a subset of relevant mutations at different prevalence thresholds and across multiple phylogenetic trees. In addition to simulated tumors with varying number of biopsies, we demonstrate the use of ClonArch on a hepatocellular carcinoma tumor with ∼280 sequencing biopsies. ClonArch provides an automated way to interactively examine the spatial clonal architecture of a tumor, facilitating clinical and biological interpretations of the spatial aspects of intra-tumor heterogeneity. Availability and implementation https://github.com/elkebir-group/ClonArch.

scholarly journals ClonArch: Visualizing the Spatial Clonal Architecture of Tumors

2020 ◽  
Author(s):  
Jiaqi Wu ◽  
Mohammed El-Kebir
Keyword(s):  
Visual Analytics ◽  
Phylogenetic Trees ◽  
Cancer Genomics ◽  
Clonal Evolution ◽  
Response To Treatment ◽  
Intratumor Heterogeneity ◽  
Tumor Evolution ◽  
Web Based ◽  
Clonal Architecture ◽  
Spatial Coordinates

AbstractMotivationCancer is caused by the accumulation of somatic mutations that lead to the formation of distinct populations of cells, called clones. The resulting clonal architecture is the main cause of relapse and resistance to treatment. With decreasing costs in DNA sequencing technology, rich cancer genomics datasets with many spatial sequencing samples are becoming increasingly available, enabling the inference of high-resolution tumor clones and prevalences across different spatial coordinates. While temporal and phylogenetic aspects of tumor evolution, such as clonal evolution over time and clonal response to treatment, are commonly visualized in various clonal evolution diagrams, visual analytics methods that reveal the spatial clonal architecture are missing.ResultsThis paper introduces ClonArch, a web-based tool to interactively visualize the phylogenetic tree and spatial distribution of clones in a single tumor mass. ClonArch uses the marching squares algorithm to draw closed boundaries representing the presence of clones in a real or simulated tumor. ClonArch enables researchers to examine the spatial clonal architecture of a subset of relevant mutations at different prevalence thresholds and across multiple phylogenetic trees. In addition to simulated tumors with varying number of biopsies, we demonstrate the use of ClonArch on a hepatocellular carcinoma tumor with ~280 sequencing biopsies. ClonArch provides an automated way to interactively examine the spatial clonal architecture of a tumor, facilitating clinical and biological interpretations of the spatial aspects of intratumor heterogeneity.Availabilityhttps://github.com/elkebir-group/ClonArch

PSiTE: a Phylogeny guided Simulator for Tumor Evolution

2019 ◽  
Vol 35 (17) ◽  
pp. 3148-3150 ◽  
Author(s):  
Hechuan Yang ◽  
Bingxin Lu ◽  
Lan Huong Lai ◽  
Abner Herbert Lim ◽  
Jacob Josiah Santiago Alvarez ◽  
...  
Keyword(s):  
Cancer Genomics ◽  
Clonal Evolution ◽  
Cell Tumor ◽  
Supplementary Information ◽  
Tumor Evolution ◽  
Supplementary Data ◽  
Efficient Tool ◽  
Wide Range ◽  
Different Types ◽  
Evolutionary Trajectories

Abstract Summary Simulating realistic clonal dynamics of tumors is an important topic in cancer genomics. Here, we present Phylogeny guided Simulator for Tumor Evolution, a tool that can simulate different types of tumor samples including single sector, multi-sector bulk tumor as well as single-cell tumor data under a wide range of evolutionary trajectories. Phylogeny guided Simulator for Tumor Evolution provides an efficient tool for understanding clonal evolution of cancer. Availability and implementation PSiTE is implemented in Python and is available at https://github.com/hchyang/PSiTE. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Inferring tumor evolution from longitudinal samples

2019 ◽  
Author(s):  
Matthew A. Myers ◽  
Gryte Satas ◽  
Benjamin J. Raphael
Keyword(s):  
Dna Sequencing ◽  
Phylogenetic Trees ◽  
Simulated Data ◽  
Lymphocytic Leukemia ◽  
Response To Treatment ◽  
Tumor Evolution ◽  
Sequencing Data ◽  
Considerable Uncertainty ◽  
Longitudinal Sampling ◽  
Clonal Composition

Background: Determining the clonal composition and somatic evolution of a tumor greatly aids in accurate prognosis and effective treatment for cancer. In order to understand how a tumor evolves over time and/or in response to treatment, multiple recent studies have performed longitudinal DNA sequencing of tumor samples from the same patient at several different time points. However, none of the existing algorithms that infer clonal composition and phylogeny using several bulk tumor samples from the same patient integrate the information that these samples were obtained from longitudinal observations. Results: We introduce a model for a longitudinally-observed phylogeny and derive constraints that longitudinal samples impose on the reconstruction of a phylogeny from bulk samples. These constraints form the basis for a new algorithm, Cancer Analysis of Longitudinal Data through Evolutionary Reconstruction (CALDER), which infers phylogenetic trees from longitudinal bulk DNA sequencing data. We show on simulated data that constraints from longitudinal sampling can substantially reduce ambiguity when deriving a phylogeny from multiple bulk tumor samples, each a mixture of tumor clones. On real data, where there is often considerable uncertainty in the clonal composition of a sample, longitudinal constraints yield more parsimonious phylogenies with fewer tumor clones per sample. We demonstrate that CALDER reconstructs more plausible phylogenies than existing methods on two longitudinal DNA sequencing datasets from chronic lymphocytic leukemia patients. These findings show the advantages of directly incorporating temporal information from longitudinal sampling into tumor evolution studies. Availability: CALDER is available at https://github.com/raphael-group.

scholarly journals Trasposon Mediated Horizontal Gene Transfer (T-HGT) of Circulating Tumor DNA Reshapes MM Clonal Architecture

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3065-3065
Author(s):  
Munevver Cinar ◽  
Steven Flygare ◽  
Marina Mosunjac ◽  
Ganji Nagaraju ◽  
Dongkyoo Park ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Drug Sensitivity ◽  
Genetic Material ◽  
Host Cells ◽  
Response To Treatment ◽  
Hierarchical Architecture ◽  
Tumor Evolution ◽  
Sequencing Analysis

Spatial genetic heterogeneity is a characteristic phenomenon that influences multiple myeloma's (MM) phenotype and drug sensitivity (Rasche L. et al and Bolli N et al.). Hence, the branch model of tumor evolution is not sufficient to explain the disorganized architecture observed in MM. In this study, we investigated whether MM ctDNA horizontal gene transfer (HGT) affect tumor genetic architecture and drug sensitivity, resembling what is seen in prokaryotes, and elucidated the mechanisms involved in the mobilization of genetic material from one cell to another. We identified that plasma from patients with MM transmits drug sensitivity or resistance to cells in culture. This transmission of drug sensitivity is mediated by ctDNA transfer of oncogenes to a host cell. Importantly, in vitro and in vivo demonstrated that ctDNA mainly targets cells resembling the cell of origin (tropism). Karyotype spreads and whole genome sequencing demonstrated that once patients ctDNA encounters host cells, it migrates into the nucleus where it ultimately integrates into the cell's genome. Integration to the genome was confirmed to be targeted to myeloma cells. Further sequencing analysis of multiple MM samples identified ctDNA tropism and integration is dependent on the 5' and 3' end presence of transposable elements (TE), particularly of the MIR and ALUsq family. These results were further validated by TE mediated delivery of GFP into MM cells in vitro and HSVTK in tumors of mouse xenografts. In conclusion, this data indicates for the first time that TE mediates MM ctDNA HGT into homologous tumor cells shaping the hierarchical architecture of tumor clones and affecting tumor response to treatment. Therapeutically, this unique quality of ctDNA can be exploited for targeted gene therapeutic approaches in MM and potentially other cancers. Disclosures Bernal-Mizrachi: Kodikas Therapeutic Solutions, Inc: Equity Ownership; TAKEDA: Research Funding; Winship Cancer Institute: Employment, Patents & Royalties.

scholarly journals Web-Based Simulation Environment for Vehicular Electrical Networks

Energies ◽  
2021 ◽  
Vol 14 (19) ◽  
pp. 6087
Author(s):  
Xavier Dominguez ◽  
Paola Mantilla-Pérez ◽  
Nuria Gimenez ◽  
Islam El-Sayed ◽  
Manuel Alberto Díaz Díaz Millán ◽  
...  
Keyword(s):  
Visual Analytics ◽  
Distribution Systems ◽  
Software Tool ◽  
Automatic Generation ◽  
Electrical Networks ◽  
Web Based ◽  
Electrical Distribution Systems ◽  
Technical Requirements ◽  
Information Interaction

For the validation of vehicular Electrical Distribution Systems (EDS), engineers are currently required to analyze disperse information regarding technical requirements, standards and datasheets. Moreover, an enormous effort takes place to elaborate testing plans that are representative for most EDS possible configurations. These experiments are followed by laborious data analysis. To diminish this workload and the need for physical resources, this work reports a simulation platform that centralizes the tasks for testing different EDS configurations and assists the early detection of inadequacies in the design process. A specific procedure is provided to develop a software tool intended for this aim. Moreover, the described functionalities are exemplified considering as a case study the main wire harness from a commercial vehicle. A web-based architecture has been employed in alignment with the ongoing software development revolution and thus provides flexibility for both, developers and users. Due to its scalability, the proposed software scheme can be extended to other web-based simulation applications. Furthermore, the automatic generation of electrical layouts for EDS is addressed to favor an intuitive understanding of the network. To favor human–information interaction, utilized visual analytics strategies are also discussed. Finally, full simulation workflows are exposed to provide further insights on the deployment of this type of computer platforms.

scholarly journals Role of liver biopsy versus non-invasive biomarkers for diagnosis of significant fibrosis and cirrhosis: a web-based survey

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohamed Alboraie ◽  
Marwa Khairy ◽  
Aisha Elsharkawy ◽  
Noha Asem ◽  
Mohamed El Kassas ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Biopsy ◽  
Hepatic Fibrosis ◽  
Serum Biomarkers ◽  
Response To Treatment ◽  
Web Based ◽  
Non Invasive ◽  
Single Method ◽  
Radiological Methods

Abstract Background Liver biopsy is the standard reference for staging hepatic fibrosis. Non-invasive methods for assessment of hepatic fibrosis and cirrhosis are becoming increasingly popular. Objective We aimed at exploring the change in practice regarding the use of liver biopsy and non-invasive methods for staging hepatic fibrosis and cirrhosis among hepatologists. Methods We performed a survey-based study that recruited hepatologists from various Egyptian institutions. Physicians were deemed eligible if they had a degree in internal medicine with hepatology as a subspecialty. We utilized an online-based survey that assessed the acceptability and reliability of liver biopsy, serum biomarkers, and radiological tools for evaluating liver fibrosis and cirrhosis. Results A total of 573 responses were retrieved (response rate = 80.3%). Out of them, 58% were having more than 15 years of experience as a hepatologist. Liver biopsy is still considered the gold standard for assessment of hepatic fibrosis and cirrhosis by 61% of participants. Liver biopsy was accepted by 44% of their patients. 84% reported the need for a more practical alternative to liver biopsy to assess disease progression or response to treatment. 78.34% of participants know serum biomarkers, 84.08% reported that they were acceptable by their patients, 37.79% thought they are reliable. 95.4% were familiar with radiological methods of non-invasive assessment of hepatic fibrosis, 89.1% reported that radiological methods were acceptable by their patients, 62% think that they are reliable and 78% reported they were applicable in clinical practice. Sixty-five percent think that combining non-invasive methods is better than using a single method. Forty percent of participants thought that radiological methods are easier to use for assessment of hepatic fibrosis followed by a combination of non-invasive methods, serum biomarkers, and liver biopsy respectively. Conclusion In conclusion, liver biopsy is still considered the most reliable method for evaluation and staging of liver cirrhosis by hepatologists in Egyptian institutions, despite the modest acceptance by the patients. Nonetheless, non-invasive methods are gaining acceptance by Egyptian physicians and patients, and most of them consider these methods as reliable and applicable tools for predicting the course of liver cirrhosis.

scholarly journals E-scape: Interactive visualization of single cell phylogenetics and spatio-temporal evolution in cancer

2016 ◽  
Author(s):  
Maia A. Smith ◽  
Cydney Nielsen ◽  
Fong Chun Chan ◽  
Andrew McPherson ◽  
Andrew Roth ◽  
...  
Keyword(s):  
Single Cell ◽  
Visual Analytics ◽  
Domain Knowledge ◽  
Treatment Resistance ◽  
Cancer Evolution ◽  
Imaging Data ◽  
Web Based ◽  
Clinical Endpoints ◽  
Cell Experiment ◽  
Spatio Temporal

Inference of clonal dynamics and tumour evolution has fundamental importance in understanding the major clinical endpoints in cancer: development of treatment resistance, relapse and metastasis. DNA sequencing technology has made measuring clonal dynamics through mutation analysis accessible at scale, facilitating computational inference of informative patterns of interest. However, currently no tools allow for biomedical experts to meaningfully interact with the often complex and voluminous dataset to inject domain knowledge into the inference process. We developed an interactive, web-based visual analytics software suite called E-scape which supports dynamically linked, multi-faceted views of cancer evolution data. Developed using R and javascript d3.js libraries, the suite includes three tools: TimeScape and MapScape for visualizing population dynamics over time and space, respectively, and CellScape for visualizing evolution at single cell resolution. The tool suite integrates phylogenetic, clonal prevalence, mutation and imaging data to generate intuitive, dynamically linked views of data which update in real time as a function of user actions. The system supports visualization of both point mutation and copy number alterations, rendering how mutations distribute in clones in both bulk and single cell experiment data in multiple representations including phylogenies, heatmaps, growth trajectories, spatial distributions and mutation tables. E-scape is open source and is freely available to the community at large.

scholarly journals Visual Comparison of Phylogenetic Trees Through iPhyloC, a New Interactive Web-based Framework

2021 ◽  
Author(s):  
Muhsen Hammoud ◽  
Charles Morphy Santos ◽  
Joao Paulo Gois
Keyword(s):  
Phylogenetic Trees ◽  
Binary Trees ◽  
Automatic Identification ◽  
Structural Comparison ◽  
Web Based ◽  
Visual Comparison ◽  
Large Trees ◽  
Cross Platform ◽  
The Common ◽  
Intuitive Design

Current side-by-side phylogenetic trees comparison frameworks face two issues: (1) accepting binary trees as input, and (2) assuming input trees having identical or highly overlapping taxa. We present a task abstraction of the problem of side-by-side comparison of two phylogenetic trees and propose a set-based measure for detailed structural comparison between two phylogenetic trees, which can be non-binary and not highly overlapping. iPhyloC is an interactive web-based framework including automatic identification of the common taxa in both trees, comparing input trees in several modes, intuitive design, high usability, scalability to large trees, and cross-platform support. iPhyloC was tested in hypothetical and real biological examples.

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