Design, modeling and in silico simulation of bacterial biosensors for detecting heavy metals in irrigation water for precision agriculture.

Sensors used in precision agriculture for the detection of heavy metals in irrigation water are generally expensive and sometimes their deployment and maintenance represent a permanent investment to keep them in operation, leaving a lasting polluting footprint in the environment at the end of their lifespan. This represents an area of opportunity to design new biological devices that can replace part, or all of the sensors currently used. In this article, a novel workflow is proposed to fully carry out the complete process of design, modeling, and simulation of reprogrammable microorganisms in silico. As a proof-of-concept, the workflow has been used to design three whole-cell biosensors for the detection of heavy metals in irrigation water, namely arsenic, mercury and lead. These biosensors are in compliance with the concentration limits established by the World Health Organization (WHO). The proposed workflow allows the design of a wide variety of completely in silico biodevices, which aids in solving problems that cannot be easily addressed with classical computing. The workflow is based on two technologies typical of synthetic biology: the design of synthetic genetic circuits, and in silico synthetic engineering, which allows us to address the design of reprogrammable microorganisms using software and hardware to develop theoretical models. These models enable the behavior prediction of complex biological systems. The output of the workflow is then exported in the form of complete genomes in SBOL, GenBank and FASTA formats, enabling their subsequent in vivo implementation in a laboratory. The present proposal enables professionals in the area of computer science to collaborate in biotechnological processes from a theoretical perspective previously or complementary to a design process carried out directly in the laboratory by molecular biologists. Therefore, key results pertaining to this work include the fully in silico workflow that leads to designs that can be tested in the lab in vitro or in vivo, and a proof-of-concept of how the workflow generates synthetic circuits in the form of three whole-cell heavy metal biosensors that were designed, modeled and simulated using the workflow. The simulations carried out show realistic spatial distributions of biosensors reacting to different concentrations (zero, low and threshold level) of heavy metal presence and at different growth phases (stationary and exponential) that are backed up by the whole design and modeling phases of the workflow.

Discovery of possible gene relationships through the application of self-organizing maps to DNA microarray databases.

DNA microarrays and cell cycle synchronization experiments have made possible the study of the mechanisms of cell cycle regulation of Saccharomyces cerevisiae by simultaneously monitoring the expression levels of thousands of genes at specific time points. On the other hand, pattern recognition techniques can contribute to the analysis of such massive measurements, providing a model of gene expression level evolution through the cell cycle process. In this paper, we propose the use of one of such techniques--an unsupervised artificial neural network called a Self-Organizing Map (SOM)-which has been successfully applied to processes involving very noisy signals, classifying and organizing them, and assisting in the discovery of behavior patterns without requiring prior knowledge about the process under analysis. As a test bed for the use of SOMs in finding possible relationships among genes and their possible contribution in some biological processes, we selected 282 S. cerevisiae genes that have been shown through biological experiments to have an activity during the cell cycle. The expression level of these genes was analyzed in five of the most cited time series DNA microarray databases used in the study of the cell cycle of this organism. With the use of SOM, it was possible to find clusters of genes with similar behavior in the five databases along two cell cycles. This result suggested that some of these genes might be biologically related or might have a regulatory relationship, as was corroborated by comparing some of the clusters obtained with SOMs against a previously reported regulatory network that was generated using biological knowledge, such as protein-protein interactions, gene expression levels, metabolism dynamics, promoter binding, and modification, regulation and transport of proteins. The methodology described in this paper could be applied to the study of gene relationships of other biological processes in different organisms.

Genetic programming as alternative for predicting development effort of individual software projects.

Statistical and genetic programming techniques have been used to predict the software development effort of large software projects. In this paper, a genetic programming model was used for predicting the effort required in individually developed projects. Accuracy obtained from a genetic programming model was compared against one generated from the application of a statistical regression model. A sample of 219 projects developed by 71 practitioners was used for generating the two models, whereas another sample of 130 projects developed by 38 practitioners was used for validating them. The models used two kinds of lines of code as well as programming language experience as independent variables. Accuracy results from the model obtained with genetic programming suggest that it could be used to predict the software development effort of individual projects when these projects have been developed in a disciplined manner within a development-controlled environment.

Use of evolved artificial regulatory networks to simulate 3D cell differentiation.

Cell differentiation has a crucial role in both artificial and natural developments. This paper presents results from simulations in which a genetic algorithm (GA) was used to evolve artificial regulatory networks (ARNs) to produce predefined 3D cellular structures through the selective activation and inhibition of genes. The ARNs used in this work are extensions of a model previously used to create 2D geometrical patterns. The GA worked by evolving the gene regulatory networks that were used to control cell reproduction, which took place in a testbed based on cellular automata (CA). After the final chromosomes were produced, a single cell in the middle of the CA lattice was allowed to replicate controlled by the ARN found by the GA, until the desired cellular structures were formed. Two simple cubic layered structures were first developed to test multiple gene synchronization. The model was then applied to the problem of generating a 3D French flag pattern using morphogenetic gradients to provide cells with positional information that constrained cellular replication.

A cell pattern generation model based on an extended artificial regulatory network.

Cell pattern generation has a fundamental role in both artificial and natural development. This paper presents results from a model in which a genetic algorithm (GA) was used to evolve an artificial regulatory network (ARN) to produce predefined 2D cell patterns through the selective activation and inhibition of genes. The ARN used in this work is an extension of a model previously used to create simple geometrical patterns. The GA worked by evolving the gene regulatory network that was used to control cell reproduction, which took place in a testbed based on cellular automata (CA). After the final chromosomes were produced, a single cell in the middle of the CA lattice was allowed to replicate controlled by the ARN found by the GA, until the desired cell pattern was formed. The model was applied to the problem of generating a French flag pattern.