Stellenbosch University

The systems biology markup language (SBML): a medium forrepresentation and exchange of biochemical network models

MOTIVATION: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. RESULTS: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. AVAILABILITY: The specification of SBML Level 1 is freely available from http://www.sbml.org/

The Systems Biology Graphical Notation

The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria

Lactoferrin is a nutrient classically found in mammalian milk. It binds iron and is transferred via a variety of receptors into and between cells, serum, bile, and cerebrospinal fluid. It has important immunological properties, and is both antibacterial and antiviral. In particular, there is evidence that it can bind to at least some of the receptors used by coronaviruses and thereby block their entry. Of importance are Heparan Sulfate Proteoglycans (HSPGs) and the host receptor angiotensin-converting enzyme 2 (ACE2), as based on other activities lactoferrin might prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from attaching to the host cells. Lactoferrin (and more specifically enteric-coated LF because of increased bioavailability) may consequently be of preventive and therapeutic value during the present COVID-19 pandemic.

The biology of ergothioneine, an antioxidant nutraceutical

Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.

Reproducible computational biology experiments with SED-ML - The Simulation Experiment Description Markup Language

BACKGROUND: The increasing use of computational simulation experiments to inform modern biological research creates new challenges to annotate, archive, share and reproduce such experiments. The recently published Minimum Information About a Simulation Experiment (MIASE) proposes a minimal set of information that should be provided to allow the reproduction of simulation experiments among users and software tools. RESULTS: In this article, we present the Simulation Experiment Description Markup Language (SED-ML). SED-ML encodes in a computer-readable exchange format the information required by MIASE to enable reproduction of simulation experiments. It has been developed as a community project and it is defined in a detailed technical specification and additionally provides an XML schema. The version of SED-ML described in this publication is Level 1 Version 1. It covers the description of the most frequent type of simulation experiments in the area, namely time course simulations. SED-ML documents specify which models to use in an experiment, modifications to apply on the models before using them, which simulation procedures to run on each model, what analysis results to output, and how the results should be presented. These descriptions are independent of the underlying model implementation. SED-ML is a software-independent format for encoding the description of simulation experiments; it is not specific to particular simulation tools. Here, we demonstrate that with the growing software support for SED-ML we can effectively exchange executable simulation descriptions. CONCLUSIONS: With SED-ML, software can exchange simulation experiment descriptions, enabling the validation and reuse of simulation experiments in different tools. Authors of papers reporting simulation experiments can make their simulation protocols available for other scientists to reproduce the results. Because SED-ML is agnostic about exact modeling language(s) used, experiments covering models from different fields of research can be accurately described and combined.

A conceptual map of invasion biology: Integrating hypotheses into a consensus network

Abstract Background and aims Since its emergence in the mid‐20th century, invasion biology has matured into a productive research field addressing questions of fundamental and applied importance. Not only has the number of empirical studies increased through time, but also has the number of competing, overlapping and, in some cases, contradictory hypotheses about biological invasions. To make these contradictions and redundancies explicit, and to gain insight into the field’s current theoretical structure, we developed and applied a Delphi approach to create a consensus network of 39 existing invasion hypotheses. Results The resulting network was analysed with a link‐clustering algorithm that revealed five concept clusters (resource availability, biotic interaction, propagule, trait and Darwin’s clusters) representing complementary areas in the theory of invasion biology. The network also displays hypotheses that link two or more clusters, called connecting hypotheses , which are important in determining network structure. The network indicates hypotheses that are logically linked either positively (77 connections of support) or negatively (that is, they contradict each other; 6 connections). Significance The network visually synthesizes how invasion biology’s predominant hypotheses are conceptually related to each other, and thus, reveals an emergent structure – a conceptual map – that can serve as a navigation tool for scholars, practitioners and students, both inside and outside of the field of invasion biology, and guide the development of a more coherent foundation of theory. Additionally, the outlined approach can be more widely applied to create a conceptual map for the larger fields of ecology and biogeography.

Reproductive biology of Australian acacias: important mediator of invasiveness?

Abstract Aim Reproductive traits are important mediators of establishment and spread of introduced species, both directly and through interactions with other life‐history traits and extrinsic factors. We identify features of the reproductive biology of Australian acacias associated with invasiveness. Location Global. Methods We reviewed the pollination biology, seed biology and alternative modes of reproduction of Australian acacias using primary literature, online searches and unpublished data. We used comparative analyses incorporating an Acacia phylogeny to test for associations between invasiveness and eight reproductive traits in a group of introduced and invasive (23) and non‐invasive (129) species. We also explore the distribution of groups of trait ‘syndromes’ between invasive and non‐invasive species. Results Reproductive trait data were only available for 126 of 152 introduced species in our data set, representing 23/23 invasive and 103/129 non‐invasive species. These data suggest that invasives reach reproductive maturity earlier (10/13 within 2 years vs. 7/26 for non‐invasives) and are more commonly able to resprout (11/21 vs. 13/54), although only time to reproductive maturity was significant when phylogenetic relationships were controlled for. Our qualitative survey of the literature suggests that invasive species in general tend to have generalist pollination systems, prolific seed production, efficient seed dispersal and the accumulation of large and persistent seed banks that often have fire‐, heat‐ or disturbance‐triggered germination cues. Conclusions Invasive species respond quicker to disturbance than non‐invasive taxa. Traits found to be significant in our study require more in‐depth analysis involving data for a broader array of species given how little is known of the reproductive biology of so many taxa in this species‐rich genus. Sets of reproductive traits characteristic of invasive species and a general ability to reproduce effectively in new locations are widespread in Australian acacias. Unless there is substantial evidence to the contrary, care should be taken with all introductions.

Comparative Biology of IncQ and IncQ-Like Plasmids

Plasmids belonging to Escherichia coli incompatibility group Q are relatively small (approximately 5 to 15 kb) and able to replicate in a remarkably broad range of bacterial hosts. These include gram-positive bacteria such as Brevibacterium and Mycobacterium and gram-negative bacteria such as Agrobacterium, Desulfovibrio, and cyanobacteria. These plasmids are mobilized by several self-transmissible plasmids into an even more diverse range of organisms including yeasts, plants, and animal cells. IncQ plasmids are thus highly promiscuous. Recently, several IncQ-like plasmids have been isolated from bacteria found in environments as diverse as piggery manure and highly acidic commercial mineral biooxidation plants. These IncQ-like plasmids belong to different incompatibility groups but have similar broad-host-range replicons and mobilization properties to the IncQ plasmids. This review covers the ecology, classification, and evolution of IncQ and IncQ-like plasmids.

FAIRDOMHub: a repository and collaboration environment for sharing systems biology research

The FAIRDOMHub is a repository for publishing FAIR (Findable, Accessible, Interoperable and Reusable) Data, Operating procedures and Models (https://fairdomhub.org/) for the Systems Biology community. It is a web-accessible repository for storing and sharing systems biology research assets. It enables researchers to organize, share and publish data, models and protocols, interlink them in the context of the systems biology investigations that produced them, and to interrogate them via API interfaces. By using the FAIRDOMHub, researchers can achieve more effective exchange with geographically distributed collaborators during projects, ensure results are sustained and preserved and generate reproducible publications that adhere to the FAIR guiding principles of data stewardship.

How wide is the “knowing-doing” gap in invasion biology?

SEEK: a systems biology data and model management platform

BACKGROUND: Systems biology research typically involves the integration and analysis of heterogeneous data types in order to model and predict biological processes. Researchers therefore require tools and resources to facilitate the sharing and integration of data, and for linking of data to systems biology models. There are a large number of public repositories for storing biological data of a particular type, for example transcriptomics or proteomics, and there are several model repositories. However, this silo-type storage of data and models is not conducive to systems biology investigations. Interdependencies between multiple omics datasets and between datasets and models are essential. Researchers require an environment that will allow the management and sharing of heterogeneous data and models in the context of the experiments which created them. RESULTS: The SEEK is a suite of tools to support the management, sharing and exploration of data and models in systems biology. The SEEK platform provides an access-controlled, web-based environment for scientists to share and exchange data and models for day-to-day collaboration and for public dissemination. A plug-in architecture allows the linking of experiments, their protocols, data, models and results in a configurable system that is available 'off the shelf'. Tools to run model simulations, plot experimental data and assist with data annotation and standardisation combine to produce a collection of resources that support analysis as well as sharing. Underlying semantic web resources additionally extract and serve SEEK metadata in RDF (Resource Description Format). SEEK RDF enables rich semantic queries, both within SEEK and between related resources in the web of Linked Open Data. CONCLUSION: The SEEK platform has been adopted by many systems biology consortia across Europe. It is a data management environment that has a low barrier of uptake and provides rich resources for collaboration. This paper provides an update on the functions and features of the SEEK software, and describes the use of the SEEK in the SysMO consortium (Systems biology for Micro-organisms), and the VLN (virtual Liver Network), two large systems biology initiatives with different research aims and different scientific communities.

Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology

Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.

Diversity, biology and evolution of IncQ-family plasmids

Harmonizing semantic annotations for computational models in biology

Life science researchers use computational models to articulate and test hypotheses about the behavior of biological systems. Semantic annotation is a critical component for enhancing the interoperability and reusability of such models as well as for the integration of the data needed for model parameterization and validation. Encoded as machine-readable links to knowledge resource terms, semantic annotations describe the computational or biological meaning of what models and data represent. These annotations help researchers find and repurpose models, accelerate model composition and enable knowledge integration across model repositories and experimental data stores. However, realizing the potential benefits of semantic annotation requires the development of model annotation standards that adhere to a community-based annotation protocol. Without such standards, tool developers must account for a variety of annotation formats and approaches, a situation that can become prohibitively cumbersome and which can defeat the purpose of linking model elements to controlled knowledge resource terms. Currently, no consensus protocol for semantic annotation exists among the larger biological modeling community. Here, we report on the landscape of current annotation practices among the COmputational Modeling in BIology NEtwork community and provide a set of recommendations for building a consensus approach to semantic annotation.

Invasion biology and conservation biology: time to join forces to explore the links between species traits and extinction risk and invasiveness

Expansion and decline of species are natural phenomena (Levin, 2000). However, owing to the increasing infl uence of humans worldwide, the processes driving expansion and decline have speeded up dramatically. Hence, we have the current biodiversity crisis. Humanmediated forces are making some species rarer (ie, driving them towards extinction) while at the same time making some species expand their ranges (‘invasive’ sensu Richardson et al., 2000). Undisputedly, the immediate causes for extinction of native species and invasiveness of aliens are extrinsic factors, such as habitat destruction and climate change. However, the ultimate causes have to be ecological and life-history characteristics of species (Kotiaho et al., 2005). Therefore, important research directions in conservation biology and invasion biology are the analyses of species traits associated with rarity (Murray et al., 2002) and invasiveness (Pyšek and Richardson, 2007), respectively. The first are important for prioritizing conservation efforts, and the second are important for prioritizing eradication efforts and the development of screening protocols of potential invasiveness of species considered for introduction to other regions. Unravelling the links between species traits and extrinsic factors is highly complex, particularly because assessment of the causes of rarity and invasiveness relies mainly on retrospective analyses since large-scale controlled experiments are often not feasible (Richardson et al., 2004). However, with the increasing availability of large, widely accessible databases and analytical approaches (eg, Wilson et al., 2007), it is becoming easier to test which traits are associated with rarity and invasiveness, and under which conditions.

MicroRNA-Regulated Networks: The Perfect Storm for Classical Molecular Biology, the Ideal Scenario for Systems Biology

A review of MRI studies in Africa with special focus on quantitative MRI: Historical development, current status and the role of medical physicists

Africa’s readiness for artificial intelligence in clinical radiotherapy delivery: Medical physicists to lead the way

BACKGROUND: There have been several proposals by researchers for the introduction of Artificial Intelligence (AI) technology due to its promising role in radiotherapy practice. However, prior to the introduction of the technology, there are certain general recommendations that must be achieved. Also, the current challenges of AI must be addressed. In this review, we assess how Africa is prepared for the integration of AI technology into radiotherapy service delivery. METHODS: To assess the readiness of Africa for integration of AI in radiotherapy services delivery, a narrative review of the available literature from PubMed, Science Direct, Google Scholar, and Scopus was conducted in the English language using search terms such as Artificial Intelligence, Radiotherapy in Africa, Machine Learning, Deep Learning, and Quality Assurance. RESULTS: We identified a number of issues that could limit the successful integration of AI technology into radiotherapy practice. The major issues include insufficient data for training and validation of AI models, lack of educational curriculum for AI radiotherapy-related courses, no/limited AI teaching professionals, funding, and lack of AI technology and resources. Solutions identified to facilitate smooth implementation of the technology into radiotherapy practices within the region include: creating an accessible national data bank, integrating AI radiotherapy training programs into Africa's educational curriculum, investing in AI technology and resources such as electronic health records and cloud storage, and creation of legal laws and policies to support the use of the technology. These identified solutions need to be implemented on the background of creating awareness among health workers within the radiotherapy space. CONCLUSION: The challenges identified in this review are common among all the geographical regions in the African continent. Therefore, all institutions offering radiotherapy education and training programs, management of the medical centers for radiotherapy and oncology, national and regional professional bodies for medical physics, ministries of health, governments, and relevant stakeholders must take keen interest and work together to achieve this goal.

Medical physics services in radiology and nuclear medicine in Africa: challenges and opportunities identified through workforce and infrastructure surveys

Abstract The International Atomic Energy Agency (IAEA) developed a staffing model to estimate the number of clinically qualified medical physicists (CQMP) that are required in an imaging facility, including diagnostic radiology and nuclear medicine. For the first time this staffing model was applied on a large scale across Africa. Within the framework of the IAEA African Regional Agreement (AFRA) Technical Cooperation (TC) project RAF6/053 entitled “Enhancing Capacity Building of Medical Physics to Improve Safety and Effectiveness of Medical Imaging (AFRA)”, a survey based on the IAEA staffing model was used to investigate the current CQMP workforce needs in imaging and radionuclide therapy in Africa in order to establish a baseline, identify gaps and suggest steps for improvement. The survey was open for five months, after which data verification was performed. 82 responses were received from 21 countries, including data from 97 diagnostic radiology and 40 nuclear medicine departments, as well as 75 interventional radiology departments and/or catheterization laboratories. Only 26·8% of centres employed an adequate number of CQMPs. The staffing model indicated that 134·3 CQMPs were required for these centres, but only 63 are currently employed in medical imaging and/or nuclear medicine at these centres. At least 11 countries do not have a single institution with an adequate number of CQMPs. Data analysis indicated that the number of radiology and nuclear medicine CQMPs is largely inadequate, at least by a factor of 20 in almost all countries in the region.

Radiation Therapy Physics Quality Assurance and Management Practices in Low- and Middle-Income Countries: An Initial Pilot Survey in Six Countries and Validation Through a Site Visit

Purpose: Our purpose was to assess physics quality assurance (QA) practices in less resourced radiation therapy (RT) centers to improve quality of care. Methods and Materials: A preliminary study was conducted in 2020 of 13 select RT centers in 6 countries, and in 2021, our team conducted onsite visits to all the RT centers in Ghana, one of the countries from the initial survey. The RT centers included 1 private and 2 public institutions (denoted as Public-1 and Public-2). Follow-up surveys were sent to 17 medical physicists from the site visit. Questions centered on the topics of equipment, institutional practice, physics quality assurance, management, and safety practices. Qualitative and descriptive methods were used for data analysis. Questions regarding operational challenges (machine downtime, patient-related issues, power outages, and staffing) were asked on a 5-point Likert scale. Results: The preliminary survey from 2020 had a 92% response rate. One key result showed that for RT centers in lower gross national income per capita countries there was a direct correlation between QA needs and the gross national income per capita of the country. The needs identified included film/array detectors, independent dose calculation software, calibration of ion chambers, diodes, thermoluminiscence diodes (TLDs), phantoms for verification, Treatment Planning System (TPS) test phantoms, imaging test phantoms and film dosimeters, education, and training. For the post survey after the site visit in 2021, we received a 100% response rate. The private and the Public-1 institutions each have computed tomography simulators located in their RT center. The average daily patient external beam workload for each clinic on a linear accelerator was: private = 25, Public-1 = 55, Public-2 = 40. The Co-60 workload was: Public-1 = 45, Public-2 = 25 (there was no Co-60 at the private hospital). Public-1 and -2 lacked the equipment necessary to conform to best practices in Task Group reports (TG) 142 and 198. Public-2 reported significant operational challenges. Notably, Public-1 and -2 have peer review chart rounds, which are attended by clinical oncologists, medical physicists, physicians, and physics trainees. All 17 physicists who responded to the post site visit survey indicated they had a system of documenting, tracking, and trending patient-related safety incidents, but only 1 physicist reported using International Atomic Energy Agency Safety in Radiation Oncology. Conclusions: The preliminary study showed a direct correlation between QA needs and the development index of a country, and the follow-up survey examines operational and physics QA practices in the RT clinics in Ghana, one of the initial countries surveyed. This will form the basis of a planned continent-wide survey in Africa intended to spotlight QA practices in low- and middle-income countries, the challenges faced, and lessons learned to help understand the gaps and needs to support local physics QA and management programs. Audits during the site visit show education and training remain the most important needs in operating successful QA programs.

Science diplomacy in medical physics – an international perspective

Physics in Africa

Africa tends to be isolated and sometimes forgotten when it comes to scientific research and in particular physics. But the region has great potential, being home to the youngest population in the world, and despite a variety of issues, there has been steady, albeit uneven progress towards establishing a scientific infrastructure. Ten African researchers discuss the diverse challenges and opportunities faced by physicists across the continent. Ten African researchers discuss the varied challenges and opportunities faced by physicists across the continent. Rabia Salihu Sa’id is a full professor of Atmospheric Physics at Bayero University, Kano, in Nigeria. She holds a PhD, MSc and BSc in Physics and an MSc in Environment and Development, and is an expert in the effects of dust aerosols on climate and air quality measurements. In 2015, she received the OWSD (Organization for Women in Science for the Developing World)/ TWAS (The World Academy of Sciences)/Elsevier Foundation Award for Early Career (Physics), which rewards and encourages women working and living in developing countries who are in the early stages of their scientific careers, having often overcome great challenges to achieve research excellence. Ibiyinka Fuwape has been a professor of physics at the Federal University of Technology, Akure, Nigeria since 1989. She is currently the Vice Chancellor of the Michael and Cecilia Ibru University, Agbarha-Otor, Delta State, Nigeria. Her research interests include theory of chaos and application of nonlinear dynamics in coupled oscillator systems, neuronal systems, and lower and upper atmospheric research. She is an alumna of the Schlumberger Faculty of the Future Fellowship programme. Alain Moise Dikandé (full professor in physics) is Head of the Physics Department, Faculty of Science, University of Buea, Cameroon. He is an Alexander von Humboldt Fellow in the ‘Experienced Researchers’ Category, a Senior Associate of the Abdus Salam International Centre for Theoretical Physics (ICTP, Trieste, Italy), guest editor of the special issue of the Journal of the Optical Society of America (JOSA A and B): Optics in Africa and member of the editorial board of Journal of Optics. Jamal Mimouni is an Algerian astrophysicist, who received his higher education between Algiers University and the United States (PhD in Particle Physics in 1985, University of Pennsylvania). He is the head of a graduate programme in astrophysics at Constantine 1 University in Algeria, and the President of the African Astronomical Society. He is an active participant in the debate on science and society in the Arab-Muslim World. Francis Hasford is the Head of Medical Physics at the University of Ghana and Ghana Atomic Energy Commission, Secretary General of the Federation of African Medical Physics Organizations, expert medical physicist for the International Atomic Energy Agency and member of the IOMP (International Organization for Medical Physics) Web Sub-committee. He received his PhD from the University of Ghana and is an associate of the International Centre for Theoretical Physics. He is the recipient of the 2016 International Union of Pure and Applied Physics (IUPAP)/IOMP Young Scientist Award in Medical Physics. Delia Haynes did her PhD at Trinity Hall at the University of Cambridge, followed by a postdoctoral fellowship with the Pfizer Institute for Pharmaceutical Materials Science, also at Cambridge. She has been at Stellenbosch University since 2007, where she is now a professor in the Department of Chemistry and Polymer Science. Delia is the chair of the Steering Committee to form the African Crystallographic Association. Irvy (Igle) Gledhill spent time at the University of California, Los Angeles and Stanford before moving to the Council for Scientific and Industrial Research in South Africa, her home country. She is now Visiting Professor of Flow Physics at the University of the Witwatersrand. She is a past president of the South African Institute of Physics and a Vice-President of the Network of African Science Academies. She edits . George Amolo is a professor of physics and Director of the School of Physics and Earth Science, The Technical University of Kenya, Nairobi, and a research associate in Computational Modelling and Materials Science with the Kenya Education Network (KENET). He received his PhD from the University of the Witwatersrand, South Africa, and worked in the University of Eldoret and Moi University, Eldoret, Kenya, before moving to the Technical University of Kenya in 2016. Omololu Akin-Ojo received his BSc and MSc Physics degrees from the University of Ibadan, and his PhD from the University of Delaware (USA). Following two postdoctoral stints at Boston University and the Abdus Salam International Centre for Theoretical Physics (ICTP) Trieste, Italy, he returned to Africa — first to Nigeria and now Rwanda as Director of the East African Institute for Fundamental Research , a physics training and research hub. His main research interest is in condensed matter physics and its applications for African development and advancement. Nashwa Eassa is an associate professor of physics and the Dean of the Deanship of Scientific Research at Al Neelain University. She undertook a postdoctoral fellowship in the Nanophotonics group at Nelson Mandela Metropolitan University (NMMU), South Africa. She holds a PhD in physics from NMMU and Master of Science in material physics and nanotechnology from Linköping University, Sweden.