RESUMO
BACKGROUND: The Biology System Description Language (BiSDL) is an accessible, easy-to-use computational language for multicellular synthetic biology. It allows synthetic biologists to represent spatiality and multi-level cellular dynamics inherent to multicellular designs, filling a gap in the state of the art. Developed for designing and simulating spatial, multicellular synthetic biological systems, BiSDL integrates high-level conceptual design with detailed low-level modeling, fostering collaboration in the Design-Build-Test-Learn cycle. BiSDL descriptions directly compile into Nets-Within-Nets (NWNs) models, offering a unique approach to spatial and hierarchical modeling in biological systems. RESULTS: BiSDL's effectiveness is showcased through three case studies on complex multicellular systems: a bacterial consortium, a synthetic morphogen system and a conjugative plasmid transfer process. These studies highlight the BiSDL proficiency in representing spatial interactions and multi-level cellular dynamics. The language facilitates the compilation of conceptual designs into detailed, simulatable models, leveraging the NWNs formalism. This enables intuitive modeling of complex biological systems, making advanced computational tools more accessible to a broader range of researchers. CONCLUSIONS: BiSDL represents a significant step forward in computational languages for synthetic biology, providing a sophisticated yet user-friendly tool for designing and simulating complex biological systems with an emphasis on spatiality and cellular dynamics. Its introduction has the potential to transform research and development in synthetic biology, allowing for deeper insights and novel applications in understanding and manipulating multicellular systems.
Assuntos
Biologia Sintética , Biologia Sintética/métodos , Modelos Biológicos , Linguagens de Programação , Biologia de Sistemas/métodos , SoftwareRESUMO
It is well known how sequencing technologies propelled cellular biology research in recent years, providing incredible insight into the basic mechanisms of cells. Single-cell RNA sequencing is at the front in this field, with single-cell ATAC sequencing supporting it and becoming more popular. In this regard, multi-modal technologies play a crucial role, allowing the possibility to simultaneously perform the mentioned sequencing modalities on the same cells. Yet, there still needs to be a clear and dedicated way to analyze these multi-modal data. One of the current methods is to calculate the Gene Activity Matrix (GAM), which summarizes the accessibility of the genes at the genomic level, to have a more direct link with the transcriptomic data. However, this concept is not well defined, and it is unclear how various accessible regions impact the expression of the genes. Moreover, the transcription process is highly regulated by the transcription factors that bind to the different DNA regions. Therefore, this work presents a continuation of the meta-analysis of Genomic-Annotated Gene Activity Matrix (GAGAM) contributions, aiming to investigate the correlation between the TF expression and motif information in the different functional genomic regions to understand the different Transcription Factors (TFs) dynamics involved in different cell types.
Assuntos
Regulação da Expressão Gênica , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica/genética , DNA/metabolismo , Genômica , GenomaRESUMO
This literature review rigorously examines the growing scientific interest in computational methods for Tissue Engineering and Regenerative Medicine biofabrication, a leading-edge area in biomedical innovation, emphasizing the need for accurate, multi-stage, and multi-component biofabrication process models. The paper presents a comprehensive bibliometric and contextual analysis, followed by a literature review, to shed light on the vast potential of computational methods in this domain. It reveals that most existing methods focus on single biofabrication process stages and components, and there is a significant gap in approaches that utilize accurate models encompassing both biological and technological aspects. This analysis underscores the indispensable role of these methods in understanding and effectively manipulating complex biological systems and the necessity for developing computational methods that span multiple stages and components. The review concludes that such comprehensive computational methods are essential for developing innovative and efficient Tissue Engineering and Regenerative Medicine biofabrication solutions, driving forward advancements in this dynamic and evolving field.