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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2016

Diagnostic assessments of student thinking about stochastic processes.

A number of research studies indicate that students often have difficulties in understanding the presence and/or the implications of stochastic processes within biological systems. While critical to a wide range of phenomena, the presence and implications of stochastic processes are rarely explicitly considered in the course of formal instruction. To help instructors identify gaps in student understanding, we have designed and tested six open source activities covering a range of scenarios, from death rates to noise in gene expression, that can be employed, alone or in combination, as diagnostics to reveal student thinking as a prelude to the presentation of stochastic processes within a course or a curriculum.

Scientific Communication and Education↗

bioRxiv2016

Illuminating Uveitis: Metagenomic Deep Sequencing Identifies Common and Rare Pathogens

BackgroundOcular infections remain a major cause of blindness and morbidity worldwide. While prognosis is dependent on the timing and accuracy of diagnosis, the etiology remains elusive in ~ 50% of presumed infectious uveitis cases.1,2 We aimed to determine if unbiased metagenomic deep sequencing (MDS) can accurately detect pathogens in intraocular fluid samples of patients with uveitis.\n\nMethodsThis is a proof-of-concept study, in which intraocular fluid samples were obtained from 5 subjects with known diagnoses, and one subject with bilateral chronic uveitis without a known etiology. Samples were subjected to MDS, and results were compared with conventional diagnostic tests. Pathogens were identified using a rapid computational pipeline to analyze the non-host sequences obtained from MDS.\n\nFindingsUnbiased MDS of intraocular fluid produced results concordant with known diagnoses in subjects with (n=4) and without (n=1) uveitis. Rubella virus (RV) was identified in one case of chronic bilateral idiopathic uveitis. The subjects strain was most closely related to a German RV strain isolated in 1992, one year before he developed a fever and rash while living in Germany.\n\nInterpretationMDS can identify fungi, parasites, and DNA and RNA viruses in minute volumes of intraocular fluid samples. The identification of chronic intraocular RV infection highlights the eyes role as a long-term pathogen reservoir, which has implications for virus eradication and emerging global epidemics.

Scientific Communication and Education↗

bioRxiv2016

Zika in Rio de Janeiro: Assessment of basic reproduction number and comparison with dengue outbreaks

Zika virus infection was declared a public health emergency of international concern in February 2016 in response to the outbreak in Brazil and its suspected link with congenital anomalies. In this study we use notification data and disease natural history parameters to estimate the basic reproduction number (R0) of Zika in Rio de Janeiro, Brazil. We also obtain estimates of R0 of dengue from time series of dengue cases in the outbreaks registered in 2002 and 2012 in the city, when DENV-3 and DENV-4 serotypes respectively, had just emerged. Our estimates of the basic reproduction number for Zika in Rio de Janeiro based on surveillance notifications (R0 = 2.33, 95% CI: 1.97 - 2.97) were higher than those obtained for dengue in the city (year 2002: R0 = 1.70 [1.50 - 2.02]; year 2012: Ro = 1.25 [1.18 - 1.36]). Given the role of Aedes aegypti as vector of both the Zika and dengue viruses, we also derive Ro of Zika as a function of both dengue reproduction number and entomological and epidemiological parameters for dengue and Zika. Using the dengue outbreaks from previous years allowed us to estimate the potential R0 of Zika. Our estimates were closely in agreement with our first Zikas R0 estimation from notification data. Hence, these results validate deriving the potential risk of Zika transmission in areas with recurring dengue outbreaks. Whether transmission routes other than vector-based can sustain a Zika epidemic still deserves attention, but our results suggest that the Zika outbreak in Rio de Janeiro emerged due to population susceptibility and ubiquitous presence of Ae. aegypti.

Scientific Communication and Education↗

bioRxiv2016

Biogeographic Ancestry and Socioeconomic Outcomes in the Americas: a Meta-analysis

Narrative reports suggest that socioeconomic status (SES) is associated with biogeographic ancestry (BGA) in the Americas. If so, SES potentially acts as a confound that needs to be taken into account when evaluating the relation between medical outcomes and BGA. To explore how systematic BGA-SES associations are, a meta-analysis of American studies was conducted. 41 studies were identified, yielding a total of 64 independent samples with directions of associations, including 48 independent samples with effect sizes. An analysis of association directions found a high degree of consistency. The square root n-weighted directions were 0.83 (K = 36), -0.81 (K = 41) and -0.82 (K = 39) for European, Amerindian and African BGA, respectively. An analysis of effect size magnitudes found that European BGA was positively associated with SES, with a meta-analytic effect size of r = .18 [95% CI: .13 to .24, K = 28, n = 35,476.50], while both Amerindian and African BGA were negatively associated with SES, having meta-analytic effect sizes of -.14 [-.18 to -.10, k =31, n = 28,937.50] and -.11 [-.15 to -.07, K = 28, n = 32,710.50], respectively. There was considerable cross-sample variation in effect sizes (mean I2 = 92%), but the sample size was not enough for performing credible moderator analysis. Implications for future studies are discussed.

Scientific Communication and Education↗

bioRxiv2016

Learning from critical care management of sheep receiving extra-corporeal membrane oxygenation for smoke-induced acute lung injury as a tool for processing large clinical datasets

BackgroundNumerous successful therapies developed for human medicine involve animal experimentation. Animal studies that are focused solely on translational potential, may not sufficiently document unexpected outcomes. Considerable amounts of data from such studies could be used to advance veterinary science. For example, sheep are increasingly being used as models of intensive care and therefore, data arising from such models must be published. In this study, the hypothesis is that there is little information describing cardiorespiratory physiological data from sheep models of intensive care and the author aimed to analyse such data to provide biological information that is currently not available for sheep that received extracorporeal life support (ECLS) following acute smoke-induced lung injury. MethodsNineteen mechanically ventilated adult ewes undergoing intensive care during evaluation of a form of ECLS (treatment) for acute lung injury were used to collate clinical observations. Eight sheep were injured by acute smoke inhalation prior to treatment (injured/treated), while another eight were not injured but treated (uninjured/treated). Two sheep were injured but not treated (injured/untreated), while one received room air instead of smoke as the injury and was not treated (placebo/untreated). The data were then analysed for 11 physiological categories and compared between the two treated groups. ResultsCompared with the baseline, treatment contributed to and exacerbated the deterioration of pulmonary pathology by reducing lung compliance and the arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ratio. The oxygen extraction index changes mirrored those of the PaO2/FiO2 ratio. Decreasing coronary perfusion pressure predicted the severity of cardiopulmonary injury. ConclusionsThese novel observations could help in understanding similar pathology such as that which occurs in animal victims of smoke inhalation from house or bush fires, aspiration pneumonia secondary to tick paralysis and in the management of the severe coronavirus disease 2019 (COVID-19) in humans.

Scientific Communication and Education↗

bioRxiv2016

A formula to estimate a Researcher’s impact by prioritizing highly cited publications

Here we suggest a new index to estimate the scientific impact of an individual researcher, namely the S-index. This index has been designed to emphasize highly cited, truly important works and to be minimally affected by poorly cited ones, without setting any arbitrary threshold. The first property makes it advantageous over the h-index, which does not discriminate between highly and moderately cited articles, while the second property - over the total number of citations, preventing the possibility of overclocking an index by publishing many trivial articles. Contrary to the h-index, which has an upper limit of the total number of publications regardless of their citation numbers, the S-index is not limited by the publication count. This allows scientists having few but very influential works to receive appropriate and respectable index values, which is impossible with the h-index. Moreover, only 10 most cited publications of an individual are typically required to calculate an S-index to 99% accuracy. Collectively, the S-index is principally different from the existing scientometric indicators and should facilitate better recognition of prominent researchers.

Scientific Communication and Education↗

bioRxiv2016

Scanning the Horizon: challenges and solutions for neuroimaging research

Functional neuroimaging techniques have transformed our ability to probe the neurobiological basis of behaviour and are increasingly being applied by the wider neuroscience community. However, concerns have recently been raised that the conclusions drawn from some human neuroimaging studies are either spurious or not generalizable. Problems such as low statistical power, flexibility in data analysis, software errors, and lack of direct replication apply to many fields, but perhaps particularly to fMRI. Here we discuss these problems, outline current and suggested best practices, and describe how we think the field should evolve to produce the most meaningful answers to neuroscientific questions.

Scientific Communication and Education↗

bioRxiv2016

A signal detection theoretic argument against claims of unmeritocratic faculty hiring

To get a faculty job, graduating doctoral students have to substantially outperform their peers, given the competitive nature of the academic job market. In an ideal, meritocratic world, factors such as prestige of degree-granting university ought not to play a substantial role. However, it has recently been reported that top-ranked universities produced about 2-6 times more faculty than did universities that were ranked lower (Clauset, Arbesman, and Larremore 2015), necessitating un-meritocratic factors: how could students from top-ranked universities be six times more productive than their peers from lower-ranked universities? Here we present a signal detection model to demonstrate that substantially higher rates of faculty production need not require substantially (and unrealistically) higher levels of student productivity. Instead, it is a high hiring threshold due to keen competition that causes small difference in average student productivity between universities to result in manifold differences in placement rates. Under this framework, the previously reported results are compatible with a purely meritocratic system. As a simple proof of concept, we examined the association between university ranking and the impact factors of students publications from a small selected sample of psychology departments in the U.S. The results are in agreement with our theoretical model. Whereas these results do not necessarily mean that the actual faculty hiring market is purely meritocratic, they highlight the difficulty in empirically demonstrating that it is not so.

Scientific Communication and Education↗

bioRxiv2016

A simple proposal for the publication of journal citation distributions

Although the Journal Impact Factor (JIF) is widely acknowledged to be a poor indicator of the quality of individual papers, it is used routinely to evaluate research and researchers. Here, we present a simple method for generating the citation distributions that underlie JIFs. Application of this straightforward protocol reveals the full extent of the skew of distributions and variation in citations received by published papers that is characteristic of all scientific journals. Although there are differences among journals across the spectrum of JIFs, the citation distributions overlap extensively, demonstrating that the citation performance of individual papers cannot be inferred from the JIF. We propose that this methodology be adopted by all journals as a move to greater transparency, one that should help to refocus attention on individual pieces of work and counter the inappropriate usage of JIFs during the process of research assessment.

Scientific Communication and Education↗

bioRxiv2016

A statistical definition for reproducibility and replicability

Everyone agrees that reproducibility and replicability are fundamental characteristics of scientific studies. These topics are attracting increasing attention, scrutiny, and debate both in the popular press and the scientific literature. But there are no formal statistical definitions for these concepts, which leads to confusion since the same words are used for different concepts by different people in different fields. We provide formal and informal definitions of scientific studies, reproducibility, and replicability that can be used to clarify discussions around these concepts in the scientific and popular press.

Scientific Communication and Education↗

bioRxiv2016

Lost dollars threaten research in public academic health centers

Decreasing federal and state support threaten long-term sustainability of research in publicly supported academic health centers. In weathering these financial threats, research at the University of California, San Francisco (UCSF) has undergone three substantial changes: (i) institutional salary support goes preferentially to senior faculty, while the young increasingly depend on grants; (ii) private and government support for research grows apace in clinical departments, but slowly declines in basic science departments; and (iii) research is judged more on its quantity (numbers of investigators and federal and private dollars) than on its goals, achievements, or scientific quality. We propose measures to alleviate these problems. Other large public academic health centers probably confront similar issues, but--except for UCSF--such centers have not been subjected to detailed public analysis.

Scientific Communication and Education↗

bioRxiv2016

Identification of Successful Mentoring Communities using Network-based Analysis of Mentor-Mentee Relationships across Nobel Laureates

Skills underlying scientific innovation and discovery generally develop within an academic community, often beginning with a graduate mentors laboratory. In this paper, a network analysis of doctoral student-dissertation advisor relationships in The Academic Tree is used to identify successful mentoring communities in high-level science, as measured by number of Nobel laureates within the community. Nobel laureates form a distinct group in the network with greater numbers of Nobel laureate ancestors, descendants, mentees/grandmentees, and local academic family. Subnetworks composed entirely of Nobel laureates extend across as many as four generations. Successful historical mentoring communities were identified centering around Cambridge University in the latter 19th century and Columbia University in the early 20th century. The current practice of building web-based academic networks, extended to include a wider variety of measures of academic success, would allow for the identification of modern successful scientific communities and should be promoted.

Scientific Communication and Education↗

bioRxiv2016

Reproducibility and replicability of rodent phenotyping in preclinical studies

The scientific community is increasingly concerned with cases of published \"discoveries\" that are not replicated in further studies. The field of mouse behavioral phenotyping was one of the first to raise this concern, and to relate it to other complicated methodological issues: the complex interaction between genotype and environment; the definitions of behavioral constructs; and the use of the mouse as a model animal for human health and disease mechanisms. In January 2015, researchers from various disciplines including genetics, behavior genetics, neuroscience, ethology, statistics and bioinformatics gathered in Tel Aviv University to discuss these issues. The general consent presented here was that the issue is prevalent and of concern, and should be addressed at the statistical, methodological and policy levels, but is not so severe as to call into question the validity and the usefulness of model organisms as a whole. Well-organized community efforts, coupled with improved data and metadata sharing, were agreed by all to have a key role to play in identifying specific problems and promoting effective solutions. As replicability is related to validity and may also affect generalizability and translation of findings, the implications of the present discussion reach far beyond the issue of replicability of mouse phenotypes but may be highly relevant throughout biomedical research.

Scientific Communication and Education↗

bioRxiv2016

Bayesian Analysis of High Throughput Data

Duplicate or triplicate experimental replicates are commonplace in the high throughput literature. However, it has not been tested whether this is statistically defensible or not. To address this issue, we use probabilistic programming to develop a simple hierarchical model for analyzing high throughput measurement data. With the model and simulated data, we show that a small increase in replicate experiments can quantitatively improve accuracy in measurement. We also provide posterior densities for statistical parameters used in the evaluation of HT data. Finally, we provide an extensible open source implementation that ingests data structured in a simple format and produces posterior densities of estimated measurement and assay evaluation parameters.

Scientific Communication and Education↗

bioRxiv2016

All or Nothing: the False Promise of Anonymity

In early 2016, the International Committee of Medical Journal Editors (ICMJE) proposed that responsible sharing of de-identified individual-level data be required for clinical trials published in their affiliated journals. There would be a delay in implementing this policy to allow for the necessary informed consents to work their way through ethical review. Meanwhile, some researchers and policy makers have conflated the notions of de-identification and anonymity. The former is a process that seeks to mitigate disclosure risk though careful application of rules and statistical analysis, while the latter is an absolute state. The consequence of confusing the process and the state is profound. Extensions to the ICMJE proposal based on the presumed anonymity of data include: sharing unconsented data; sharing data without managing access, as Open Data; and proposals to sell data. This essay aims to show that anonymity (the state) cannot be guaranteed by de-identification (the process), and so these extensions to the ICMJE proposal should be rejected on governance grounds, if no other. This is not as negative a position as it might seem, as other disciplines have been aware of these limitations and concomitant responsibilities for many years. The essay concludes with an example from social science of managed access strategies that could be adopted by the medical field.

scientific communication and education↗

bioRxiv2016

Starting from the end: what to do when restricted data is released

Repository managers can never be one hundred percent sure of the security ofhosted research data. Even assuming that human errors and technical faults will never happen, repositories can be subject to hacking attacks. Therefore, repositories accepting personal/sensitive data (or other forms of restricted data) should have workflows in place with defined procedures to be followed should things go wrong and restricted data is inappropriately released. In this paper wewill report on our considerations and procedures when restricted data from ourinstitution was inappropriately released.

scientific communication and education↗

bioRxiv2016

Copyright and the Use of Images as Biodiversity Data

1.Taxonomy is the discipline responsible for charting the worlds organismic diversity, understanding ancestor/descendant relationships, and organizing all species according to a unified taxonomic classification system. Taxonomists document the attributes (characters) of organisms, with emphasis on those can be used to distinguish species from each other. Character information is compiled in the scientific literature as text, tables, and images. The information is presented according to conventions that vary among taxonomic domains; such conventions facilitate comparison among similar species, even when descriptions are published by different authors.\n\nThere is considerable uncertainty within the taxonomic community as to how to re-use images that were included in taxonomic publications, especially in regard to whether copyright applies. This article deals with the principles and application of copyright law, database protection, and protection against unfair competition, as applied to images. We conclude that copyright does not apply to most images in taxonomic literature because they are presented in a standardized way and lack the creativity that is required to qualify as 'copyrightable works'. There are exceptions, such as wildlife photographs, drawings and artwork produced in a distinctive individual form and intended for other than comparative purposes (such as visual art). Further exceptions may apply to collections of images that qualify as a database in the sense of European database protection law. In a few European countries, there is legal protection for photographs that do not qualify as works in the usual sense of copyright. It follows that most images found in taxonomic literature can be re-used for research or many other purposes without seeking permission, regardless of any copyright declaration. In observance of ethical and scholarly standards, re-users are expected to cite the author and original source of any image that they use.

scientific communication and education↗

bioRxiv2016

Ten simple rules for structuring papers

Good scientific writing is essential to career development and to the progress of science. A well-structured manuscript allows readers and reviewers to get excited about the subject matter, to understand and verify the papers contributions, and to integrate these contributions into a broader context. However, many scientists struggle with producing high-quality manuscripts and typically get little training in paper writing. Focusing on how readers consume information, we present a set of 10 simple rules to help you get across the main idea of your paper. These rules are designed to make your paper more influential and the process of writing more efficient and pleasurable.

scientific communication and education↗