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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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2020

The Costs and Benefits of a Modified Biomedical Science Workforce

Analyses of the biomedical research workforce, the biomedical research enterprise and its sustainability have identified a number of threats and offered many solutions to alleviate the problems. While, a number of these solutions have been implemented, one solution that has not been broadly adopted, despite being widely recommended, is to increase the number of staff scientists and reduce dependency on trainees. The perceived impediment of this is the cost. This paper explores the costs associated with laboratory personnel and the benefits, in terms of productivity, associated with different positions in the workforce. The results of this cost-benefit analysis depend upon the values assigned to different metrics of productivity by individuals and institutions. If first and senior author publications are the most important metrics of productivity, a trainee dependent workforce is much more cost effective. If total publications is the most valued metric of productivity, the cost effectiveness of trainee and staff scientists is reasonably equitable. This analysis provides data for consideration when making personnel decisions and for the continued discussion of modification of the biomedical research workforce. It also provides insight into the incentives for modification of the workforce at the grass roots, which must be considered by institutions genuinely committed to workforce modification to sustain the biomedical research enterprise.

scientific communication and education↗

bioRxiv2020

Robust Preclinical Evidence in Somatic Cell Genome Editing: A Key Driver of Responsible and Efficient Therapeutic Innovations

Somatic cell genome editing (SCGE) is highly promising for therapeutic innovation. Multifold financial and academic incentives exist for the quickest possible translation from preclinical to clinical studies. This study demonstrates that the majority of 46 preclinical SCGE studies discussed in expert reviews as particularly promising for clinical translation do not report on seven key elements for robust and confirmatory research practices: (1) randomization, (2) blinding, (3) sample size calculation, (4) data handling, (5) pre-registration, (6) multi-centric study design, and (7) independent confirmation. Against the background of the high incentives for clinical translation and recent concerns about the reproducibility of published preclinical evidence, we present the here examined reporting standards (1-4) and the new NIH funding criteria for SCGE research (6-7) as a viable solution to protect this promising field from backlashes. We argue that the implementation of the novel methodological standards, e.g. "confirmation" and "pre-registration", is promising for preclinical SCGE research and provides an opportunity to become a lighthouse example for trust-worthy and useful translational research.

scientific communication and education↗

bioRxiv2020

Reporting quality of trend analyses in leading medicine and oncology journals

Reporting quality of clinical research is critical for evidence-based medicine and reproducibility of clinical research. Most of the works focused on reporting quality of clinical trials and observational longitudinal studies. However, few focused on that of trend analyses. The reporting of recommended statistic metrics in trend analyses was also largely unclear. Therefore, we examined reporting quality of the trend analyses based on reporting of recommended statistic metrics. We systemically searched the PubMed for the trend-analysis articles published in 10 leading medicine and oncology journals during the 11 years from 2008 to 2018. The studies published after 2019 were not included due to the sudden, significant increase of publication number during and immediately after the COVID-19 pandemic. Only original articles, research letters and meta-analyses/systematic reviews were included. We scored the reporting quality of these articles based on whether they reported p-values/effect-sizes, and beta/co-efficient/slope/annual-percentage-change (APC). There were 297 qualified articles, among which 193 (66.0%) and 216 (72.7%) articles reported P-value and effect-size, respectively. Only 13 (5.8%) analyses reported neither p-value/effect size nor beta/coefficient/slope/APC. In multivariable regression models, author affiliation of epidemiology department was associated with less reporting effect-size, but that of statistics department with more reporting. Interestingly, U.S. senior-authors (versus non-U.S.) more likely reported p-values. No factors were independently linked to reporting APC. The reporting quality of trend analyses in leading medicine and oncology journals appear moderate and should be further improved. We thus call for more research and awareness of reporting-quality in trend analyses in oncology research and beyond.

scientific communication and education↗

bioRxiv2020

Co-Citation Percentile Rank and JYUcite: a new network-standardized output-level citation influence metric and its implementation using Dimensions API

Judging value of scholarly outputs quantitatively remains a difficult but unavoidable challenge. Most of the proposed solutions suffer from three fundamental shortcomings: they involve i) the concept of journal, in one way or another, ii) calculating arithmetic averages from extremely skewed distributions, and iii) binning data by calendar year. Here, we introduce a new metric Co-citation Percentile Rank (CPR), that relates the current citation rate of the target output taken at resolution of days since first citable, to the distribution of current citation rates of outputs in its co-citation set, as its percentile rank in that set. We explore some of its properties with an example dataset of all scholarly outputs from University of Jyvaskyla spanning multiple years and disciplines. We also demonstrate how CPR can be efficiently implemented with Dimensions database API, and provide a publicly available web resource JYUcite, allowing anyone to retrieve CPR value for any output that has a DOI and is indexed in the Dimensions database. Finally, we discuss how CPR remedies failures of the Relative Citation Ratio (RCR), and remaining issues in situations where CPR too could potentially lead to biased judgement of value.

scientific communication and education↗

bioRxiv2020

Incidence of canine dilated cardiomyopathy, breed and age distributions, and grain-free diet sales in the United States from 2000-2019: A retrospective survey.

BackgroundDilated cardiomyopathy (DCM) is considered a predominantly inherited disease in dogs. Recent reports suggest an increased incidence of DCM in atypical breeds eating grain-free and/or legume-rich diets. However, little data regarding incidence of DCM within the US is available; and no existing data quantifies DCM among breeds over time. HypothesisWe hypothesized that DCM incidence among breeds could be estimated by retrospective polling of veterinary cardiologists. Further, if a correlation existed between grain-free diets and DCM, an increase in DCM would be on trend with increased grain-free pet food sales. Materials and MethodsThirty-six U.S. cardiology specialty practices were asked for all initial canine and DCM cases evaluated from 2000-2019; fourteen cardiology practices participated. DCM signalment data was provided by three hospitals over 15 years; representing 68 breeds. Age distribution of DCM cases upon diagnosis were compared to other cardio cases and general hospital population from one hospital. All data were evaluated using linear regression models. Grain-free pet food sales data was evaluated from 2011-2019. ResultsFourteen hospitals participated and reported 67,243 unique canine patients. Nationally, data did not support a significant change in percent DCM over time (p=0.85). The overall average incidence rate of DCM during the study period was 3.83% (range 2.41-5.65%), while grain-free diet sales increased 500% from 2011-2019. No correlation between overall DCM incidence and grain free diet sales was discovered. A significant upward trend in mixed breeds diagnosed with DCM, with no significant trend in other breeds was appreciated. An upward trend in age at DCM diagnosis was identified, correlating with trends from overall hospital populations. ConclusionsThese data do not support overall increased DCM incidence, or a correlation with grain-free pet food sales. Additional data are necessary to understand whether regional factors contribute to increased DCM within smaller cohorts.

scientific communication and education↗

bioRxiv2020

Measuring effects of trainee professional development on research productivity: A cross-institutional meta-analysis

PhD-trained scientists are essential contributors to the workforce in diverse employment sectors that include academia, industry, government, and non-profit organizations. Hence, best practices for training the future biomedical workforce are of national concern. Complementing coursework and laboratory research training, many institutions now offer professional training that enables career exploration and develops a broad set of skills critical to various career paths. The National Institutes of Health funded academic institutions to design innovative programming to enable this professional development through a mechanism known as Broadening Experiences in Scientific Training (BEST). Programming at the BEST awardee institutions included career panels, skill-building workshops, job-searching workshops, site visits, and internships. An initial concern was since doctoral training is lengthy and requires focused attention on dissertation research, having students participate in additional complementary training activities might lengthen time to degree and hamper student research productivity. To address this concern, using time to degree and publication records as measures of efficiency and productivity, metrics were analyzed from ten BEST awardee institutions. Comparing doctoral students who participated to those who did not, results revealed that across these diverse academic institutions, there were no differences in time to degree or manuscript output. Furthermore, a few institutions even demonstrated a positive correlation between participation in career and professional development activities and productivity. Our findings suggest that doctoral students should be encouraged to participate in career and professional development opportunities to ensure their preparedness for a variety of diverse and important careers in the workforce. Significance StatementOur study is unique in that it compiled doctoral degree durations at ten different universities, recorded individual participation in career and professional development activities in terms of dosage, and tracked individual engagement in real-time rather than relying on surveys sent to trainees after graduation. Participation in career and professional development activities, including internships, did not decrease efficiency or productivity. Our findings suggest that doctoral students should be encouraged to participate in career and professional development opportunities to ensure their preparedness for a variety of diverse and important careers in the workforce.

scientific communication and education↗

bioRxiv2020

Benchmarking ensemble docking methods as a scientific outreach project

The discovery of new drugs is a time consuming and expensive process. Methods such as virtual screening, which can filter out ineffective compounds from drug libraries prior to expensive experimental study, have become popular research topics. As the computational drug discovery community has grown, in order to benchmark the various advances in methodology, organizations such as the Drug Design Data Resource have begun hosting blinded grand challenges seeking to identify the best methods for ligand pose-prediction, ligand affinity ranking, and free energy calculations. Such open challenges offer a unique opportunity for researchers to partner with junior students (e.g., high school and undergraduate) to validate basic yet fundamental hypotheses considered to be uninteresting to domain experts. Here, we, a group of high school-aged students and their mentors, present the results of our participation in Grand Challenge 4 where we predicted ligand affinity rankings for the Cathepsin S protease, an important protein target for autoimmune diseases. To investigate the effect of incorporating receptor dynamics on ligand affinity rankings, we employed the Relaxed Complex Scheme, a molecular docking method paired with molecular dynamics-generated receptor conformations. We found that CatS is a difficult target for molecular docking and we explore some advanced methods such as distance-restrained docking to try to improve the correlation with experiments. This project has exemplified the capabilities of high school students when supported with a rigorous curriculum, and demonstrates the value of community-driven competitions for beginners in computational drug discovery.

scientific communication and education↗

bioRxiv2020

The impact of preprint servers in the formation of novel ideas

We study whether novel ideas in biomedical literature appear first in preprints or traditional journals. We develop a Bayesian method to estimate the time of appearance for a phrase in the literature, and apply it to a number of phrases, both automatically extracted and suggested by experts. We see that presently most phrases appear first in the traditional journals, but there is a number of phrases with the first appearance on preprint servers. A comparison of the general composition of texts from bioRxiv and traditional journals shows a growing trend of bioRxiv being predictive of traditional journals. We discuss the application of the method for related problems.

scientific communication and education↗

bioRxiv2020

Current practices in scientific poster preparation: survey results

Posters are intended to spark scientific dialogue and omnipresent at biological conferences. Guides and how-to articles help life scientists in preparing informative visualizations in poster format. However, those posters shown at conferences are at present often overloaded with data and text and are poorly designed, which in sum hinder, rather than spark communication. Here, we surveyed life scientists themselves to understand why posters are such a struggle and to shed light on poster preparation from their subjective perspectives. We find that biologist spend on average two entire days preparing one poster, with half of the time devoted to visual design aspects. Most respond that they receive no design or software training and also receive little to no feedback when preparing their visualizations. In conclusion, our data suggests that some training, beyond providing literature, of life scientists in visualization principles and tools would likely improve conference poster quality. In addition, this would also improve other common visuals such as figures and slides, and thus overall benefit the science communication of researchers.

scientific communication and education↗

bioRxiv2020

Psychiatric Genomics Research During the COVID-19 Pandemic: A Survey of Psychiatric Genomics Consortium Researchers

Between April 20, 2020 and June 19, 2020 we conducted a survey of the membership of the Psychiatric Genomics Consortium (PGC) to explore the impact of COVID-19 on their research and academic careers. A total of 123 individuals responded representing academic ranks from trainee to full professor, tenured and fixed-term appointments, and all genders. The survey included both quantitative and free text responses. Results revealed considerable concern about the impact of COVID-19 on research with the greatest concern reported by individuals in non-permanent positions and female researchers. Concerns about the availability of funding and the impact of the pandemic on career progression were commonly reported by early career researchers. We provide recommendations for institutions, organizations such as the PGC, as well as individual senior investigators to ensure that the futures of early career investigators, especially those underrepresented in academic medicine such as women and underrepresented minorities, are not disproportionately disadvantaged by the COVID-19 pandemic.

scientific communication and education↗

bioRxiv2020

From amazing work to I beg to differ - analysis of bioRxiv preprints that received one public comment till September 2019

While early commenting on studies is seen as one of the advantages of preprints, the nature of such comments, and the people who post them, have not been systematically explored. We analysed comments posted between 21 May 2015 and 9 September 2019 for 1,983 bioRxiv preprints that received only one comment. Sixty-nine percent of comments were posted by non-authors (n=1,366), and 31% by preprint authors (n=617). Twelve percent of non-author comments (n=168) were full review reports traditionally found during journal review, while the rest most commonly contained praises (n=577, 42%), suggestions (n=399, 29%), or criticisms (n=226, 17%). Authors comments most commonly contained publication status updates (n=354, 57%), additional study information (n=158, 26%), or solicited feedback for the preprints (n=65, 11%). Our study points to the value of preprint commenting, but further studies are needed to determine the role that comments play in shaping preprint versions and eventual journal publications.

scientific communication and education↗

bioRxiv2020

A Structured Professional Development Curriculum for Postdoctoral Fellows Leads to Recognized Knowledge Growth

Postdoctoral training enables research independence and professional readiness. National reports have emphasized professional development as a critical component of this training period. In response, many institutions are establishing transferable skills training workshops for postdocs; however, the lack of structured programs and an absence of methods to assess outcomes beyond participant satisfaction surveys are critical gaps in postdoctoral training. To address these shortcomings, we took the approach of structured programming and developed a method for controlled assessment of outcomes. Our program You3 (You, Your Team, Your Project), co-designed by postdoctoral fellows, focused on a structured array of management and leadership skills agnostic of ultimate career path(s). We then measured outcomes in a controlled manner, by systematically comparing perceived knowledge and growth of participants with non-participants as the control group. You3 participants discern greater growth, independent of number of years in training, in competencies overall compared to the control group. This growth was shown by multiple criteria including self-reporting and associative analysis. Correspondingly, You3 participants reported greater knowledge in 75% of the modules when compared to controls. These data indicate that structured learning, where postdocs commit to a curriculum via a cohort-structure, leads to positive outcomes and provides a framework for programs to assess outcomes in a rigorous manner.

scientific communication and education↗

bioRxiv2020

Nanoscape, a data-driven 3D real-time interactive virtual cell environment

Knowledge of cellular and structural biology has reached unprecedented levels of detail. In conjunction with advances in 3D computer visualisation techniques this has allowed exploration of cellular ultrastructure and environments by a virtual user. The extraction and integration of relevant scientific information, along with consideration of the best representation of data, is often a bottleneck in the visualisation process for many 3D biomedical artists. Here we introduce Nanoscape, a collaborative project between 3D computer artists, computer graphics developers, and cell biologists that enables a user to navigate a cell in a complex 3D computer visualised environment. We combine actual data from various scientific disciplines (including structural biology, cell biology and multiple microscopic techniques) and apply artistic expression and design aesthetics to create a unique new experience where a real-time virtual explorer can traverse a cell surface, observe and interact with a more scientifically accurate cell surface environment.

scientific communication and education↗

bioRxiv2020

The data-index: an author-level metric that values impactful data and incentivises data sharing

Author-level metrics are a widely used measure of scientific success. The h-index, and its variants, measure publication output (number of publications) and impact (number of citations), and these are often used to allocate funding or jobs. Here we argue that the emphasis on publication output and impact hinders progress in the fields of ecology and evolution as it disincentivises two fundamental practices: generating long-term datasets and sharing data. We describe a new author-level metric, the data-index, which values dataset output and impact and promotes generating and sharing data as a result. It is designed to complement other metrics of scientific success, as scientific contributions are diverse and our value system should reflect that. Future work should focus on designing alternative metrics that value our wider merits, such as communicating our research, informing policy, mentoring other scientists, and providing open-access code and tools.

scientific communication and education↗

bioRxiv2020

Digital Imaging and Vision Analysis in Science Project improves the self-efficacy and skill of undergraduate students in computational work

In many areas of science, the ability to use computers to process, analyze, and visualize large data sets has become essential. The mismatch between the ability to generate large data sets and the computing skill to analyze them is arguably the most striking within the life sciences. The Digital Image and Vision Applications in Science (DIVAS) project describes a scaffolded series of interventions implemented over the span of a year to build the coding and computing skill of undergraduate students majoring primarily in the natural sciences. The program is designed as a community of practice, providing support within a network of learners. The program focus, images as data, provides a compelling hook for participating scholars. Scholars begin the program with a one-credit spring semester seminar where they are exposed to image analysis. The program continues in the summer with a one-week, intensive Python and image processing workshop. From there, scholars tackle image analysis problems using a pair programming approach and finish the summer with independent research. Finally, scholars participate in a follow-up seminar the following spring and help onramp the next cohort of incoming scholars. We observed promising growth in participant self-efficacy in computing that was maintained throughout the project as well as significant growth in key computational skills. DIVAS program funding was able to support seventeen DIVAS over three years, with 76% of DIVAS scholars identifying as women and 14% of scholars being members of an underrepresented minority group. Most scholars (82%) entered the program as freshmen, with 89% of DIVAS scholars retained for the duration of the program and 100% of scholars remaining a STEM major one year after completing the program. The outcomes of the DIVAS project support the efficacy of building computational skill through repeated exposure of scholars to relevant applications over an extended period within a community of practice.

scientific communication and education↗

bioRxiv2020

Positive outcomes of COVID-19 research-related gender policy changes

The COVID-19 pandemic has exposed and exacerbated gender biases in science, technology, engineering, mathematics, and medicine. Accumulating evidence suggests that female scientists productivity dropped during the initial lockdown period. With more time being spent on caregiving responsibilities, women may be struggling to collaborate on grant applications and launch new experiments. Scientists with disabilities or who belong to Indigenous nations or communities of color may have less time to devote to research due to health, family, or community needs. Collateral damage in this situation, the appropriate integration of sex, gender, and other identity characteristics in research content may also suffer. Sex and gender are better attended to when female scientists form part of the research team. Research funding agencies have a role to play in mitigating these effects by putting in place gender equity policies that support all applicants and ensure research quality. Accordingly, a national health research funder implemented gender policy changes that included extending deadlines and factoring sex and gender into COVID-19 grant requirements. Following these changes, the funder received more applications from female scientists, awarded a greater proportion of grants to female compared to male scientists, and received and funded more grant applications that considered sex and gender in the content of COVID-19 research. Whether or not these strategies will be sufficient in the long-term to prevent widening of the gender gap in science, technology, engineering, mathematics and medicine requires continued monitoring and oversight. Further work is urgently required to mitigate inequities associated with identity characteristics beyond gender.

scientific communication and education↗

bioRxiv2020

Modelling disease transmission from touchscreen user interfaces

The extensive use of touchscreens for all manner of human-computer interactions has made them plausible instruments of touch-mediated disease transmission. To that end, we employ stochastic simulations to model human-fomite interaction with a distinct focus on touchscreen interfaces. The timings and frequency of interactions from within a closed population of infectious and susceptible individuals was modelled using a basic queuing network. A pseudo reproductive number (R) was used to compare outcomes under various parameter conditions. We also expanded the simulation to a specific real-world scenario; namely airport self check-in and baggage drop. Results revealed that the required rate of cleaning/disinfecting of screens to effectively mitigate R can be inordinately high. This suggests that revised or alternative methods should be considered.

scientific communication and education↗

bioRxiv2020

Gender stereotype and the scientific career of women: Evidence from biomedical research centers

Women are underrepresented in the top ranks of the scientific career, including the biomedical disciplines. This is not generally the result of explicit and easily recognizable gender biases but the outcome of decisions with many components of unconscious nature that are difficult to assess. Evidence suggests that implicit gender stereotypes influence perceptions as well as decisions. To explore these potential reasons of womens underrepresentation in life sciences we analyzed the outcome of gender-science and gender-career Implicit Association Tests (IAT) taken by 2,589 scientists working in high profile biomedical research centers. We found that male-science association is less pronounced among researchers than in the general population (34% below the level of the general population). However, this difference is mostly explained by the low level of the IAT score among female researchers. Despite the highly meritocratic view of the academic career, male scientists have a high level of male-science association (261% the level among women scientists), similar to the general population.

scientific communication and education↗