What Can Time-Series Gene Expression Analysis do for my System?

Gene Expression Analysis can provide an ideal blend of high-level analysis and granular detail when studying a biological system. We know that the RNA levels of an organism’s genes not only determine the system’s overall status, but also the functioning of the many molecular pathways in the organism.  We also know that activity in these pathways can make or break a commercial product or production process. Let’s see how Time-Series Gene Expression Analysis can address these challenges.

The key is to is to look at the dynamics in gene expression, this means studying the ways in which gene expression changes during a biological process.  As the price of RNA-seq data has come down, it has become very feasible to analyze time series RNA-seq data from organisms in commercial biological products and industrial production processes.  The focus then is on deploying tools and expertise to use the information contained in the tens of thousands of data points that these time series experiments produce, to understand and control the mechanisms in critical pathways and processes.

Mimetics’ clients bring us the following general types of challenges.

Discovery: In many systems, the pathways or upstream triggers for pathway activation for critical are not known, even when an organism has been developed and a  desired trait or product has been successfully produced. In these cases experiments are needed to observe, analyze, and model the gene expression patterns that lead to the phenotype or pathway of interest. The analysis captures the upstream activators and pathways that lead to the phenotype as well as those that inhibit the process. Looking at the dynamics of the entire genome, computational tools can identify the pathways of interest along with co-regulated genes, upstream positive and negative regulators, and then show how those regulators are modified. Having a context-specific and time-specific regulatory landscape enables a focus in on pathways of interest, while also showing how that process sits within the organism and its environment, revealing how either or both of these could be modified to improve the outcome.

Creation: When a proven workhorse organism has shown time and again that it is an excellent chassis for production or growth, it is compelling to introduce heterologous gene expression into these robust organisms to generate a novel product or to drive a new trait. Unfortunately, various hurdles can arise where endogenous biology prevents the heterologous processes from being effectively utilized. Enter gene expression analysis. Using endogenous pathways as a guide for gene expression timing, level, and phasing, modeling can offer multiple suggestions for coupling heterologous gene expression to endogenous promoter usage, transcription factors, and genomic locations. Grafting production of heterologous genes into existing efficient expression pathways allows for precision, tunable expression at the proper time during a biological process.

Calibration: Organisms that produce the desired trait or product are not valuable, if they cannot be used in a commercially viable production process.  Gene expression analysis can discover incompatibilities between stress, proliferation, or growth pathways and the organism’s growth conditions, environment, or the population of cohabitating organisms. In some cases, transcription, translation, or trafficking processes are hindered in time or growth condition dependant ways. Modeling the regulation of the targeted pathway, as well as those regulating cellular machinery, can provide a roadmap for improving production processes and trait expression.

Intellectual Property: Critical to the business strategy of any company in biological production is protection of the intellectual property protection in their engineered strains. Discovery, selection, or directed evolution of an organism capable of generating the desired product is a first step, but it may not lead to patentable results. Gene expression analysis can help discover how the newly developed organism behaves and provide guidance toward the engineering of a strain with equivalent or even enhanced performance. The engineered strain can be patent protected and continue to generate value and ROI for our clients for the long term.

With proper experimental design and the right analytical tools, gene expression analysis can help to solve very difficult challenges in bringing new products to market and in improving existing products. Whether it is in ag-tech, fermentation for production, or in biotech/pharma and whether the product is a crop plant, a microbe, or any substance produced by a microbe or cell line (protein, enzyme, biochemical), success in product and process development relies on the expression of the correct genes at the correct time. Sometimes, critical genes need their expression timing or level to be optimized; in other cases, inhibitory or competing pathways become activated that prevent effective or timely production. Time-series gene expression analysis can help to solve these problems in ways that toher techniques cannot.  Mimetics’ deploys tools that are built to capture global gene expression data across entire biological processes and interpret the data to deliver maximum value.