Laboratory Biologists Research Articles

External Quality Assessment Program for Next-Generation Sequencing-Based HIV Drug Resistance Testing: Logistical Considerations.

Next-generation sequencing (NGS) is likely to become the new standard method for HIV drug resistance (HIVDR) genotyping. Despite the significant advances in the development of wet-lab protocols and bioinformatic data processing pipelines, one often-missing critical component of an NGS HIVDR assay for clinical use is external quality assessment (EQA). EQA is essential for ensuring assay consistency and laboratory competency in performing routine biomedical assays, and the rollout of NGS HIVDR tests in clinical practice will require an EQA. In September 2019, the 2nd International Symposium on NGS HIVDR was held in Winnipeg, Canada. It convened a multidisciplinary panel of experts, including research scientists, clinicians, bioinformaticians, laboratory biologists, biostatisticians, and EQA experts. A themed discussion was conducted on EQA strategies towards such assays during the symposium. This article describes the logistical challenges identified and summarizes the opinions and recommendations derived from these discussions, which may inform the development of an inaugural EQA program for NGS HIVDR in the near future.

Bioinformatics: Novel Insights from Genomic Information.

While scientific methods have dominated research approaches in biology over the past decades, it is increasingly recognized that the complexity of biological systems must be addressed by a different approach, namely unbiased research involving the collection of large amounts of genome-wide information. To enable analysis of this information we and others are developing a variety of computational tools that allow bioinformaticists and wet laboratory biologists to extract novel patterns of data from these results and generate novel biological insights while generating new hypotheses for testing in the laboratory. There are two types of critical tools, databases to collate all information on biomolecules, especially interactions, and tools that reorganize information in a supervised (e.g. pathway analysis or gene ontology) or unsupervised (nonhierarchical clustering and network analysis) manner. Here we describe some of the tools we have developed and how we have used these to gain new ideas in the general area of infection and innate immunity/inflammation. In particular, it is illustrated how such analyses enable novel hypotheses about mechanisms associated with diseases and the mechanisms of action of immunomodulatory and other interventions, the definition of mechanism-based biomarkers/diagnostics, and prospective new interventions based on drug repurposing.

Group planarian sudden mortality: Is the threshold around global geomagnetic activity ≥K6?

Sudden deaths in groups of animals have been observed by field and laboratory biologists. We have measured mortalities in large group-housed planarian during the infrequent periods of very intense geomagnetic activity. In 13 separate episodes over the last 5 y we have observed the sudden death in our laboratory of hundreds of planarian if their density was about 1 worm per cc and the global geomagnetic activity was K≥6 the day before or the day of the observation of the mortality. Such mortality never occurred in other conditions or days. Both estimates of the "magnetic moment" of a planarian in magnetic fields above this threshold of sustained magnetic flux density as well as the magnetic energy within the planarian volume predict values that could affect phenomenon associated with the total numbers of pH-dependent charges within each worm. These conditions could affect the Levin-Burr bioelectrical signals and networks that affect patterning information and sustainability in whole living systems. The establishment of a central reservoir for the report of these transient events might allow Life Scientists to more fully appreciate the impact of these pervasive global stimuli upon dense groups of animals.

Using Immune Marker Panels to Evaluate the Role of Inflammation in Cancer: Summary of an NCI-sponsored Workshop.

Chronic inflammation is recognized to play a role in the development of several cancers. Past investigations of inflammation and cancer have typically been small, used varied assay platforms, and included a narrow range of analytes. Multiplex technologies have now been developed to measure larger numbers of inflammatory markers using small volumes of specimens. This has created an opportunity for systematic, large-scale epidemiological studies to evaluate the role of inflammation in cancer. However, lack of consensus on the approach to these studies, the technologies/assays to be used, and the most adequate analysis/interpretation of findings have thus far hindered progress. In June of 2014, the National Cancer Institute convened a workshop involving epidemiologists, immunologists, statisticians, and laboratory biologists to share their experiences with new inflammation marker technologies and findings from association studies using such methods and technologies (http://epi.grants.cancer.gov/workshops/). Consensus and gaps in our understanding of the role of chronic inflammation in cancer were identified and recommendations made to improve future efforts in this area. These recommendations are summarized herein, along with specific suggestions for how they may be implemented. By facilitating discussions among various groups, and encouraging interdisciplinary collaborations, we anticipate that the pace of research in this field will be accelerated and duplication of efforts can be minimized.

Morphology and Sexual Dimorphism of the Many-Lined Skink in North Central New Mexico

Abstract. In 2001 and 2002, a study of many-lined skinks (Plestiodon multivirgatus) was conducted by Los Alamos National Laboratory biologists in north-central New Mexico to determine means and ranges for several morphological characters and to test for sexual dimorphism. Over both years, there were 539 new captures of many-lined skinks, which included 131 Hatchlings. The earliest hatchling capture was on 19 June and the latest capture was on 31 August. Hatchling captures peaked on 1 August in 2001 and 6 August in 2002. The age class, sex, snout—vent length (SVL), tail length (TL), mass, head length (HL), and head width (HW) were recorded and individuals were released at the point of capture. Our results indicate that the SVL, mass, HL, and HW did not exhibit sexual dimorphism. The sex ratio was skewed toward females in this study. It is not known whether the many-lined skink has sexual determination based on environmental factors, but the data here suggest that more research is needed. From these observa...

Building Better Institutions

What is the best way to promote innovative research? How can we build research institutions of the future that will promote cross-disciplinary interactions among young creative minds? Despite the recent growth in scientific knowledge, conventional disciplinebased methods have not been sufficiently effective at developing new understanding and treatments. Researchers need to be encouraged to identify important questions and tackle them with multidisciplinary approaches. Contemporary biomedical research has to integrate biological, nonbiological, and clinical disciplines, and its application requires interactions with hospital and commercial partners. This can be facilitated by research institutions with an environment that supports strong interdisciplinary interactions between scientists: a place where laboratory biologists are encouraged to collaborate with clinical researchers to understand the medical implications of their work, with pharmaceutical companies for the translation of discoveries into treatments, and with physical scientists to expand their thinking and repertoire of experimental approaches. Such an institution must be continually open to new ideas and permeable to interactions with outside researchers and organizations.

GenScalpel: An Application for Sequence Retrieval and Extraction from the GenBank flatfile

GenScalpel is a program designed for the retrieval and extraction of specified sequences from large-scale sequence sets in NCBI GenBank flatfile format. This routine task in bioinformatics analysis is a pressing need for laboratory biologists. Another objective of application development is to respond to the new form of the NCBI Nucleotide Sequence Database, which was updated in November 2011. In addition to a powerful sequence refinement application, GenScalpel provides convenient functions for web-based sequence downloading or multiple files batch processing. This note discusses major applications of the program and includes example data sets to demonstrate its performance. The program is written in PERL. GenScalpel, including installation packages for Windows and Linux systems as well as the accompanying documentation, are available free of charge at http://genscalpel.biosv.com/.

ChemChains: a platform for simulation and analysis of biochemical networks aimed to laboratory scientists

BackgroundNew mathematical models of complex biological structures and computer simulation software allow modelers to simulate and analyze biochemical systems in silico and form mathematical predictions. Due to this potential predictive ability, the use of these models and software has the possibility to compliment laboratory investigations and help refine, or even develop, new hypotheses. However, the existing mathematical modeling techniques and simulation tools are often difficult to use by laboratory biologists without training in high-level mathematics, limiting their use to trained modelers.ResultsWe have developed a Boolean network-based simulation and analysis software tool, ChemChains, which combines the advantages of the parameter-free nature of logical models while providing the ability for users to interact with their models in a continuous manner, similar to the way laboratory biologists interact with laboratory data. ChemChains allows users to simulate models in an automatic fashion under tens of thousands of different external environments, as well as perform various mutational studies.ConclusionChemChains combines the advantages of logical and continuous modeling and provides a way for laboratory biologists to perform in silico experiments on mathematical models easily, a necessary component of laboratory research in the systems biology era.

Artemis and ACT: viewing, annotating and comparing sequences stored in a relational database

Motivation: Artemis and Artemis Comparison Tool (ACT) have become mainstream tools for viewing and annotating sequence data, particularly for microbial genomes. Since its first release, Artemis has been continuously developed and supported with additional functionality for editing and analysing sequences based on feedback from an active user community of laboratory biologists and professional annotators. Nevertheless, its utility has been somewhat restricted by its limitation to reading and writing from flat files. Therefore, a new version of Artemis has been developed, which reads from and writes to a relational database schema, and allows users to annotate more complex, often large and fragmented, genome sequences.Results: Artemis and ACT have now been extended to read and write directly to the Generic Model Organism Database (GMOD, http://www.gmod.org) Chado relational database schema. In addition, a Gene Builder tool has been developed to provide structured forms and tables to edit coordinates of gene models and edit functional annotation, based on standard ontologies, controlled vocabularies and free text.Availability: Artemis and ACT are freely available (under a GPL licence) for download (for MacOSX, UNIX and Windows) at the Wellcome Trust Sanger Institute web sites: http://www.sanger.ac.uk/Software/Artemis/ http://www.sanger.ac.uk/Software/ACT/Contact: artemis@sanger.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.

A multidimensional approach for detecting species patterns in Malagasy vertebrates

The biodiversity of Madagascar is extraordinarily distinctive, diverse, and endangered. It is therefore urgent that steps be taken to document, describe, interpret, and protect this exceptional biota. As a collaborative group of field and laboratory biologists, we employ a suite of methodological and analytical tools to investigate the vertebrate portion of Madagascar's fauna. Given that species are the fundamental unit of evolution, where micro- and macroevolutionary forces converge to generate biological diversity, a thorough understanding of species distribution and abundance is critical for understanding the evolutionary, ecological, and biogeographic forces that have shaped Malagasy vertebrate diversity. We illustrate the means by which we apply Mayr's "three basic tasks" of the systematist [Mayr, E. (1942) Systematics and the Origin of Species from the Viewpoint of a Zoologist (Harvard Univ. Press, Cambridge, MA)] to identify, classify, and study the organisms that together constitute Madagascar's vertebrate community. Using field inventory methods, specimen-based studies, and morphological and molecular analyses, we formulate hypotheses of species identity that then serve as the foundation for subsequent studies of biology and history. Our experience, as well as that of other investigators, has shown that much of the vertebrate species diversity in Madagascar is "cryptic" for both biological and practical reasons. Beyond issues of cryptic biological diversity, the resolution of species identity in Madagascar has been hampered because of a lack of vouchered comparative material at the population level. Through our activities, we are attempting to remedy these limitations while simultaneously enhancing research capacity in Madagascar.

Amateurs and professionals in one county: Biology and natural history in late Victorian Yorkshire

My goals in this paper are twofold: to outline there fashioning of amateur and professional roles in life science in late Victorian Yorkshire, and to provide a revised historiography of the relationship between amateurs and professionals in this era. Some historical treatments of this relationship assume that amateurs were demoralized by the advances of laboratory science, and so ceased to contribute and were left behind by the autonomous “new biology.” Despite this view, I show that many amateurs played a vital part in the construction of a professional academic community in urban Yorkshire, and then continued to collaborate with the laboratory-based biologists. The key to any analysis of the relationship between amateurs and professionals is the great variety of amateur identities and practices in Victorian Yorkshire. The amateur-professional riftfallacy arose because laboratory biologists fashioned an identity in conscious opposition to a particular type of amateur: an ideal that belied an array of co-operative relationships. As naturalists refashioned their roles and identities in light of the changes within academe and without, debates about the practice and place of life science took place as often among amateurs as between professionals and amateurs.

Life as it could be: Alife attempts to simulate evolution

Artificial life (Alife) explores natural life by attempting to create biological phenomena in computers and other nonliving media. Alife also strives to introduce a broader, more universal understanding of life (accessible to new kinds of manipulation and testing), than that defined by traditional biology. Looked at in this way, Alife represents the flip side of the empirical-analytic approach of most laboratory biologists, who start with a whole organism, deconstruct it into its component parts (for example organs, tissues, cells, genes, molecules, and so on), and then try to derive its fundamental principles. Most biologists would prefer to be able to simply reverse engineer life and synthesize real organisms, cookbook style, from their basic ingredients, but so far, this feat has eluded them. It is concluded that however it is viewed, Alife has not only spawned some fascinating varieties of digital life, but also an exciting new field of research. Moreover, Alife has engendered a rich and provocative body of thought, whether you're for or against it, with the potential for generating an endless number of new ideas.

Model Organisms in Evolutionary Studies

Mendel used peas. Morgan used Dro? sophila. Delbruck used T4 phages. The idea was to learn about the general by studying the particular, to use a specific organism as a model for all others. The approach has been unquestionably powerful and suc? cessful. Laboratory-based studies of molec? ular and cellular biology have come to dominate the field of biology, using a handful of familiar laboratory models: Escherichia coli, yeast, maize, Arabidopsis (a cabbage relative), Drosophila, Caenorhab? ditis (nematode), Xenopus, and mouse. These are commonly thought of as the model or? ganisms. The result has been a very large community of scientists using a very small group of organisms to answer questions fundamental to much of biology. In systematics, by contrast, a relatively small group of scientists studies a very large number of organisms. The importance of model organisms to systematists, and of systematics to laboratory biologists who rely on model organisms as research tools, has never really been explored. Yet it seems clear that there should be much common

The Loeb-Jennings debate and the science of animal behavior.

American laboratory biologists showed considerable interest in the study of invertebrate behavior in the period 1890–1910. The most important controversy was that between Jacques Loeb and H. S. Jennings regarding the nature of animal tropisms. Loeb advocated a dynamic approach that would lead to control of behavior, while Jennings argued for structural-mechanical explanations designed to account for evolutionary adaptation. Jennings's criticism of Loeb's tropism theory was a Pyrrhic victory in that it led American biologists to lose interest in invertebrate behavior. The paper concludes by considering the relative impact of Leob's and Jennings's research programs on the work of John B. Watson.