A calibrated agent-based computer model of stochastic cell dynamics in normal human colon crypts useful for in silico experiments

Gattaca provides the first base-pair resolution artificial genomes for tracking somatic mutations within agent based modeling. Through the incorporation of human reference genomes, mutational context, sequence coverage/error information Gattaca is able to realistically provide comparable sequence data for in-silico comparative evolution studies with human somatic evolution studies. This user-friendly method, incorporated into each in-silico cell, allows us to fully capture somatic mutation spectra and evolution.

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Colonic Saturated Fatty Acid Concentrations and Expression of COX-1, but not Diet, Predict Prostaglandin E2in Normal Human Colon Tissue

Nutrition and Cancer ◽

10.1080/01635581.2016.1213866 ◽

2016 ◽

Vol 68 (7) ◽

pp. 1192-1201 ◽

Cited By ~ 5

Author(s):

ElKhansa Sidahmed ◽

Ananda Sen ◽

Jianwei Ren ◽

Arsh Patel ◽

D. Kim Turgeon ◽

...

Keyword(s):

Fatty Acid ◽

Saturated Fatty Acid ◽

Human Colon ◽

Colon Tissue ◽

Normal Human ◽

Cox 1

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Isolation, Characterization, and Agent-Based Modeling of Mesenchymal Stem Cells in a Bio-construct for Myocardial Regeneration Scaffold Design

Data ◽

10.3390/data4020071 ◽

2019 ◽

Vol 4 (2) ◽

pp. 71 ◽

Cited By ~ 1

Author(s):

Diana Victoria Ramírez López ◽

María Isabel Melo Escobar ◽

Carlos A. Peña-Reyes ◽

Álvaro J. Rojas Arciniegas ◽

Paola Andrea Neuta Arciniegas

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

In Silico ◽

Cardiac Tissue ◽

Cellular Level ◽

Cell Behavior ◽

Agent Based Model ◽

Agent Based ◽

And Migration

Regenerative medicine involves methods to control and modify normal tissue repair processes. Polymer and cell constructs are under research to create tissue that replaces the affected area in cardiac tissue after myocardial infarction (MI). The aim of the present study is to evaluate the behavior of differentiated and undifferentiated mesenchymal stem cells (MSCs) in vitro and in silico and to compare the results that both offer when it comes to the design process of biodevices for the treatment of infarcted myocardium in biomodels. To assess in vitro behavior, MSCs are isolated from rat bone marrow and seeded undifferentiated and differentiated in multiple scaffolds of a gelled biomaterial. Subsequently, cell behavior is evaluated by trypan blue and fluorescence microscopy, which showed that the cells presented high viability and low cell migration in the biomaterial. An agent-based model intended to reproduce as closely as possible the behavior of individual MSCs by simulating cellular-level processes was developed, where the in vitro results are used to identify parameters in the agent-based model that is developed, and which simulates cellular-level processes: Apoptosis, differentiation, proliferation, and migration. Thanks to the results obtained, suggestions for good results in the design and fabrication of the proposed scaffolds and how an agent-based model can be helpful for testing hypothesis are presented in the discussion. It is concluded that assessment of cell behavior through the observation of viability, proliferation, migration, inflammation reduction, and spatial composition in vitro and in silico, represents an appropriate strategy for scaffold engineering.

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Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles

Gut ◽

10.1136/gutjnl-2019-320019 ◽

2020 ◽

Vol 69 (12) ◽

pp. 2165-2179 ◽

Cited By ~ 4

Author(s):

Helen H N Yan ◽

Hoi Cheong Siu ◽

Siu Lun Ho ◽

Sarah S K Yue ◽

Yang Gao ◽

...

Keyword(s):

Transcriptome Analysis ◽

Early Onset ◽

Human Colon ◽

Normal Colon ◽

Normal Human ◽

Cell Transcriptome ◽

Molecular Phenotypes ◽

Single Cell Transcriptome ◽

Genetic Profiles ◽

Early Onset Colorectal Cancer

ObjectiveSporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank enriched in EOCRCs.DesignWe established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC. Exome and transcriptome analysis was performed.ResultsWe observed a striking diversity of molecular phenotypes, including PTPRK-RSPO3 fusions. Transcriptionally, RSPO fusion organoids resembled normal colon organoids and were distinct from APC mutant organoids, with high BMP2 and low PTK7 expression. Single cell transcriptome analysis confirmed the similarity between RSPO fusion organoids and normal organoids, with a propensity for maturation on Wnt withdrawal, whereas the APC mutant organoids were locked in progenitor stages. CRISPR/Cas9 engineered mutation of APC in normal human colon organoids led to upregulation of PTK7 protein and suppression of BMP2, but less so with an engineered RNF43 mutation. The frequent co-occurrence of RSPO fusions with SMAD4 or BMPR1A mutation was confirmed in TCGA database searches. RNF43 mutation was found in organoid from a leukaemia survivor with a novel mutational signature; and organoids with POLE proofreading mutation displayed ultramutation. The cancer organoid genomes were stable over long culture periods, while normal human colon organoids tended to be subject to clonal dominance over time.ConclusionsThese organoid models enriched in EOCRCs with linked genomic data fill a gap in existing CRC models and reveal distinct genetic profiles and novel pathway cooperativity.

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