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Morphogenesis software based on epigenetic code concept.

ABSTRACT: The process of morphogenesis is an evolution of shape of an organism together with the differentiation of its parts. This process encompasses numerous biological processes ranging from embryogenesis to regeneration following crisis such as amputation or transplantation. A fundamental theoretical question is where exactly do these instructions for (re-)construction reside and how are they implemented? We have recently proposed a set of concepts, aiming to respond to these questions and to provide an appropriate mathematical formalization of the geometry of morphogenesis [1]. First, we consider a possibility that the evolution of shape is determined by epigenetic information, responsible for realization of different types of cell events. Second, we suggest a set of rules for converting this epigenetic information into instructive signals for cell event for each cell, as well as for transforming it after each cell event. Next we give notions of cell state, determined by its epigenetic array, and cell event, which is a change of cell state, and formalize development as a graph (tree) of cell states connected by 5 types of cell events, corresponding to the processes of cell division, cell growth, cell death, cell movement and cell differentiation. Here we present a Morphogenesis software capable to simulate an evolution of a 3D embryo starting from zygote, following a set of rules, based on our theoretical assumptions, and thus to provide a proof-of-concept of the hypothesis of epigenetic code regulation. The software creates a developing embryo and a corresponding graph of cell events according to the zygotic epigenetic spectrum and chosen parameters of the developmental rules. Variation of rules influencing the resulting shape of an embryo may help elucidating the principal laws underlying pattern formation.

SUBMITTER: Bessonov N

PROVIDER: S-EPMC6806383 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Morphogenesis software based on epigenetic code concept.

Bessonov Nikolay N Butuzova Oksana O Minarsky Andrey A Penner Robert R Soulé Christophe C Tosenberger Alen A Morozova Nadya N

Computational and structural biotechnology journal 20190903

The process of morphogenesis is an evolution of shape of an organism together with the differentiation of its parts. This process encompasses numerous biological processes ranging from embryogenesis to regeneration following crisis such as amputation or transplantation. A fundamental theoretical question is where exactly do these instructions for (re-)construction reside and how are they implemented? We have recently proposed a set of concepts, aiming to respond to these questions and to provide ...[more]

PMID: 31666938

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Project description:Immense phenotypic variability exists among healthy individuals which is a consequence of both genetic and environmental effects. Genome wide expression variability is a powerful tool for capturing these expression variations and hence can give insights into genotype phenotype correlations. In the ancient Indian system of medicine, of Ayurveda, the basic tenet for treatment relies on phenotypic assessment In this system, assessment of predisposition, susceptibility or prognosis for disease is based on the phenotypic assessment of the individual. Each individuals has a basic constitution which is termed as Prakriti, majorly decided by the relative concentration of three constituents called doshas - Vata (kinetic) Pitta (metabolic) and Kapha (structural) at the time of fertilization. Phenotypically, depending on the concentration the normal individuals can be classified onto 7 basic types of which 3 are more distinct and are called as Pure Prakriti and the rest of the 4 groups are of mixed types. Pure Prakriti individuals have one of the doshas in more prominence than the other. In this study individuals of Pure Prakrities have been selected for elucidation of the transcriptomic variation in peripheral whole blood cells. Keywords: Gene expression variability within healthy individuals, subgrouped on the basis of Prakriti (basic constitution of an individual based on Ayurveda) Healthy individuals of pure prakriti (as described in Ayurveda) of age between 18-40 years were identified, using a questionnaire (for objective assessment) developed, by qualified Ayurvedic practitioners. The individuals have been primarily assessed for phenotypic difference based on morphological characteristics / physiology along with some subjective assessment of physical capabilities and aptitudes. The individuals have been classified as â??Vataâ?? (V), â??Pittaâ?? (P) and â??Kaphaâ??(K) prakriti. The individuals were provided a similar diet 3 hours prior to sample collection with no interim intake of food or smoking in between. In order to find gene expression differences between V, P and K cDNA microarray experiment was performed in pooled samples wherein males and females experiments were carried out separately. We performed loop design experiments , where each prakriti was compared with the other two. Technical replicates involving dye swap for each prakriti was used in the same experiment. We present results of 4 biological replicates and 4 technical replicates of each prakriti in females, and 3 biological and 3 technical replicates of each prakriti in males. Total RNA was isolated from whole blood cells of volunteers using EZ-RNA isolation kit (Biological Industries) as per manufacturers protocol. Double stranded cDNA was synthesized from 15 Âµg (5 Âµg each sample) of total RNA using Microarray cDNA Synthesis Kit (Roche). The cDNA was purified using Micorarray Target Purification Kit (Roche), according to the manufacturerâ??s protocol. Each pool of Vata, Pitta and Kapha purified cDNA was divided into two halves, one half labeled with Cy5 and other with Cy3 (Amersham Biosciences) using Microarray RNA Target Synthesis Kit T7 (Roche) and labeled products were purified by Microarray Target Purification Kit (Roche). The two cRNA samples of each biological replicate, one labeled with Cy3 and another with Cy5, were pooled together, precipitated, washed and air-dried. The dried pellet was dissolved in RNAase free water (Sigma). Hybridization solution was prepared by mixing hybridization buffer (DIG Easy Hyb; Roche), 10mg/ml salmon testis DNA (0.05 mg/ml final concentration, Sigma) and 10mg/ml yeast tRNA (0.05 mg/ml final concentration, Sigma) and added to the labeled product. This mixture was denatured at 65ÂºC and applied onto cDNA microarray slides. Inter prakriti cohybridization was carried out at 37ÂºC for 16 hrs. The 48 Ã? 20 Ã? 20 (19,200 spots) human single spot 19K cDNA microarray was procured from University Health Network Microarray Centre, Toronto, Canada. Coverslips were removed by submerging the slides in a solution containing 1X SSC and 0.1% SDS at 50ÂºC. Slides were washed in 1X SSC and 0.1% SDS (three times for 15 minutes each) in a coplin jar at 50ÂºC with occasional swirling and then transferred to 1X SSC and washed with gentle swirling at room temperature (twice for 15 minutes each). Finally, slides were washed in 0.1X SSC for 15 minutes and then liquid was quickly removed from the slide surface by spinning at 600 rpm for 5 minutes. Microarray slides were scanned at 10Âµm resolution in GenePix 4000A Microarray Scanner (Molecular Devices), using both green and red lasers. The 16 bit TIFF images were preprocessed and quantified using Gene Pix Pro 6.0 software (Molecular Devices). Analysis was carried out taking two experiments at a time, separately for male and female data. Background subtracted mean values were used for the analysis. All the negative values were removed and only those genes having positive values for all the samples were considered for further analysis. Values were log2 transformed and lowess normalization was applied to remove dye bias. Across array normalization was carried out using quantile normalization method to correct for systematic variation between arrays. One-way analysis of variance was adopted to identify differentially expressed genes in all three categories. F-test was carried out in order to reject the hypothesis of equality of three group means. in order to investigate further the nature of differentially expressed genes; we have drawn strip charts and carried out pair wise comparisons using t-test. p-values obtained from ANOVA have been adjusted for multiplicity using Bonferroni method for controlling family wise error rate. Genes at pï?£0.1 level of significance were considered to be significantly different in expression between all three groups.

Project description:BackgroundLeft ventricular assist device (LVAD) implantation significantly impacts on a recipient's symptoms and quality of life. Capturing their experiences and post implant journey is an important part of clinical practice, research and device design evolution. Patient reported outcome measures (PROMs) are a useful tool for capturing that experience. However, patient reported outcome measures need to reflect recipients' experiences. Discussions with a patient partner group found that none of the frequently used cardiology PROMs captured their unique experiences.AimsTo capture the experiences and important issues for LVAD recipients. Develop a conceptual map of domains and items that should be reflected in patient reported outcomes.MethodsGroup concept mapping (GCM) web-based software was used to remotely capture and structure recipients' experiences across a wide geographical area. GCM is a semi-quantitative mixed method consisting of 3 stages: item generation, item sorting and rating (importance, relevance and frequency). Patient partners were involved in all aspects of the study design and development.Results18 LVAD recipients consented to take part. 101 statements were generated and multi-dimensional scaling, and hierarchical cluster analysis identified 9 clusters. Cluster themes included: Activities, Partner/family support, Travel, Mental wellbeing, Equipment and clothing, Physical and cognitive limitations, LVAD Restrictions, LVAD Challenges and positive impact of the LVAD (LVAD Positives). LVAD Positives were scored highest across all the rating variables, e.g., frequency (2.85), relevance (2.44) and importance (2.21). Other domains rated high for importance included physical and cognitive limitations (2.19), LVAD restrictions (2.11), Partner/family support (2.02), and Equipment and clothing (2.01).ConclusionOnline GCM software facilitated the inclusion of geographically dispersed recipients and provided useful insights into the experiences of LVAD recipients. The conceptual framework identifies important domains and items that should be prioritised and included in patient reported outcomes in future research, LVAD design evolution, and clinical practice.

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Morphogenesis software based on epigenetic code concept.

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Morphogenesis software based on epigenetic code concept.

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