Bayesian calibration,process modeling and uncertainty quantification in biotechnology

High-throughput experimentation has revolutionized data-driven experimental sciences and opened the door to the application of machine learning techniques. Nevertheless, the quality of any data analysis strongly depends on the quality of the data and specifically the degree to which random effects in the experimental data-generating process are quantified and accounted for. Accordingly calibration, i.e. the quantitative association between observed quantities and measurement responses, is a core element of many workflows in experimental sciences.Particularly in life sciences, univariate calibration, often involving non-linear saturation effects, must be performed to extract quantitative information from measured data. At the same time, the estimation of uncertainty is inseparably connected to quantitative experimentation. Adequate calibration models that describe not only the input/output relationship in a measurement system but also its inherent measurement noise are required. Due to its mathematical nature, statistically robust calibration modeling remains a challenge for many practitioners, at the same time being extremely beneficial for machine learning applications.In this work, we present a bottom-up conceptual and computational approach that solves many problems of understanding and implementing non-linear, empirical calibration modeling for quantification of analytes and process modeling. The methodology is first applied to the optical measurement of biomass concentrations in a high-throughput cultivation system, then to the quantification of glucose by an automated enzymatic assay. We implemented the conceptual framework in two Python packages, calibr8 and murefi, with which we demonstrate how to make uncertainty quantification for various calibration tasks more accessible. Our software packages enable more reproducible and automatable data analysis routines compared to commonly observed workflows in life sciences.Subsequently, we combine the previously established calibration models with a hierarchical Monod-like ordinary differential equation model of microbial growth to describe multiple replicates of Corynebacterium glutamicum batch cultures. Key process model parameters are learned by both maximum likelihood estimation and Bayesian inference, highlighting the flexibility of the statistical and computational framework.     

Challenging the empire

This paper considers how Paul Gilroy transformed hitherto dominant understandings of the relationship between race and class by developing an innovative account that foregrounded questions of racist oppression and collective resistance amid the organic crisis of British capitalism. The returns from this rethinking were profound in that he was able to make transparent both the structuring power of racism within the working class, and the necessity for autonomous black resistance. At the same time, significant lacunae in his account are identified, including the neglect of the episodic emergence of working-class anti-racism and the part played by socialists, particularly those of racialized minority descent in fashioning a major anti-racist social movement. The paper concludes with a lament for the disappearance of such work informed by a ‘Marxism without guarantees’ in the contemporary field of racism studies, and asks readers to consider the gains to be derived from such a re-engagement.     

The greening of biotechnology: the growth of the US biotechnology industry

The growth and advancement of biotechnology worldwide has been the focus of many studies, and at the heart of this advancement has been a new industry of small biotechnology firms in the United States. Since the early 1970s more than 300 small companies have been founded in the United States to work with the new technologies of genetic engineering, monoclonal antibody production, and in related areas. In addition, many major corporations in the United States have sought entry into biotechnology. Hundreds of new companies have been founded to interact with the biotechnology firms and large corporations, supplying reagents, equipment, fermentation expertise and serving a variety of other ancillary functions. Nowhere else in the world has a biotechnology industry been initiated to such a large degree. Today, the average US biotechnology firm is six to seven years old. The current state of the US biotechnology industry, historical perspectives, major trends and some future outlooks will be described below.     

Pharmaceutical biotechnology: Chemical biotechnology: Web alert

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Biotechnology.     

Regulation of biotechnology in the United States: One and a half years of using the 'coordinated framework'

There are several organizations in the US with responsibilities for regulatory oversight of the planned introduction of recombinant DNA organisms into the environment. Equally, there are many kinds of projects which require assessment. The policies, recommendations and rulings of the various authorities have been integrated into a 'Coordinated Framework' which defines the operation of flexible case-by-case risk assessment. Additions to and revision of the guidelines are being made, a process which will continue in the light of new experience.     

Innovation and the regulation of products of agricultural biotechnology in the United States of America

The policy of the United States government is to seek regulatory approaches, consistent with applicable laws, that protect health and the environment while reducing unnecessary regulatory burdens and avoiding unjustifiably inhibiting innovation, stigmatizing new technologies, or creating unnecessary trade barriers [Adapted from the National Strategy for Modernizing the Regulatory System for Biotechnology Products, Product of the Emerging Technologies Interagency Policy Coordination Committee’s Biotechnology Working Group (OSTP 2016)]. U.S. agencies are focused on delivering health and environmental protection based on the best available science; establishing transparent, coordinated, predictable, and efficient regulatory practices across agencies; and promoting public confidence in the oversight of the products of biotechnology through clear and transparent public engagement [Adapted from the Task Force on Agriculture and Rural Prosperity Report (USDA 2017)]. U.S. agencies that regulate the products of agricultural biotechnology discuss regulatory approaches presented during the June 2018 OECD Conference on Genome Editing Applications in Agriculture, focusing on plants developed using genome editing.

     

Pharmaceutical biotechnology, Chemical biotechnology: Web alert

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Biotechnology.     

Environmental biotechnology: the ongoing quest

Environmental biotechnology, until now, has primarily focused on the development of technologies to treat aqueous, solid and gaseous wastes. At present, the basic knowledge on how biotechnology can handle these wastes has been acquired and the focus is now on the implementation of these processes as 'best available technology not entailing excessive costs' (BATNEEC) in the framework of strict and transparent environmental legislation. New environmental challenges continue to evolve, as it becomes clear that waste streams should be tackled in an overall holistic way. New technologies to reach this goal are currently under development. Novel aspects with respect to the domain of water treatment are, for example, the biomembrane reactor technology and the newly discovered processes to remove nitrogen by means of anaerobic ammonium oxidation. Also, most challenging is the continuing strive for re-use of treated wastewater. Indeed, water shortage is emerging in an increasing number of countries all over the world and necessitates the short cycling of water. Finally, biotechnology has a key role to play in the novel approaches to design wastewater treatment based on decentralised sanitation and reuse (DESAR). Solid waste is a major challenge worldwide. The implementation of anaerobic digestion to treat biowastes has become a grown-up technology. New approaches in which biotechnological processes are linked to physical processes, such as plasma technology, certainly deserve special attention for the coming decades. Soil and sediment clean up by means of biostimulation/remediation/augmentation is now well established. Certainly, a number of prospects need to be further explored, such as the use of special energy sources to stimulate in situ the microbial community and the seeding of knowledge to the in situ community by means of horizontal gene transfer mechanisms. A number of waste gases can be handled by biofilter systems. Biological treatment of wastegases is also evolving, inasmuch as that besides conventional chemical pollutants, now also highly problematic chemicals (even dioxins) can be dealt with through proper biotechnological approaches. A remarkable new potential is the use of well designed probiotics to upgrade aquaculture and together with conventional biological water treatment processes, to guarantee the overall water quality of this domain of food production.     

Barrels XXXI comes to the inland empire

The 31st annual Barrels meeting was held on the campus of the University of California, Riverside on the first two days of November, 2018. The meeting focuses on the whisker to cortical barrel pathway and the systems it impacts. This year’s meeting focussed on the neural mechanisms of motor control, the functions of higher order thalamic nuclei and adaptable perception and decision-making.