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“There is no problem that a library card can't solve” according to author Eleanor Brown [1]. This advice is sound, probably for both life and science, but even the best tool (like the library) is most effective when accompanied by instructions and a basic understanding of how and when to use it. For many budding scientists, the first day in a new lab setting often involves a stack of papers, an email full of links to pertinent articles, or some promise of a richer understanding so long as one reads enough of the scientific literature. However, the purpose and approach to reading a scientific article is unlike that of reading a news story, novel, or even a textbook and can initially seem unapproachable. Having good habits for reading scientific literature is key to setting oneself up for success, identifying new research questions, and filling in the gaps in one’s current understanding; developing these good habits is the first crucial step. Advice typically centers around two main tips: read actively and read often. However, active reading, or reading with an intent to understand, is both a learned skill and a level of effort. Although there is no one best way to do this, we present 10 simple rules, relevant to novices and seasoned scientists alike, to teach our strategy for active reading based on our experience as readers and as mentors of undergraduate and graduate researchers, medical students, fellows, and early career faculty. Rules 1–5 are big picture recommendations. Rules 6–8 relate to philosophy of reading. Rules 9–10 guide the “now what?” questions one should ask after reading and how to integrate what was learned into one’s own science.

Dengue, a mosquito-borne infectious disease caused by the dengue viruses, is present in many parts of the tropical and subtropical regions of the world. All four serotypes of dengue viruses are endemic in Singapore, an equatorial city-state. Frequent outbreaks occur, sometimes leading to national epidemics. However, few studies have attempted to characterize breakpoints which precede large rises in dengue case counts. In this paper, Bayesian regime switching (BRS) models were employed to infer epidemic and endemic regimes of dengue transmissions, each containing regime specific autoregressive processes which drive the growth and decline of dengue cases, estimated using a custom built multi-move Gibbs sampling algorithm. Posterior predictive checks indicate that BRS replicates temporal trends in Dengue transmissions well and nowcast accuracy assessed using a post-hoc classification scheme showed that BRS classification accuracy is robust even under limited data with the AUC-ROC at 0.935. LASSO-based regression and bootstrapping was used to account for plausibly high dimensions of climatic factors affecting Dengue transmissions, which was then estimated using cross-validation to conduct statistical inference on long-run climatic effects on the estimated regimes. BRS estimates epidemic and endemic regimes of dengue in Singapore which are characterized by persistence across time, lasting an average of 20 weeks and 66 weeks respectively, with a low probability of transitioning away from their regimes. Climate analysis with LASSO indicates that long-run climatic effects up to 20 weeks ago do not differentiate epidemic and endemic regimes. Lastly, by fitting BRS to simulated disease data generated from a stochastic Susceptible-Infected-Recovered model, mechanistic links between infectivity and regimes classified using BRS were provided. The model proposed could be applied to other localities and diseases under minimal data requirements where transmission counts over time are collected., Author summary Dengue, a mosquito-borne infectious disease caused by the dengue viruses, is present in many parts of the tropical and subtropical regions of the world. All four serotypes of dengue viruses are endemic in Singapore, an equatorial city-state. Frequent outbreaks occur, sometimes leading to national epidemics. However, few studies have attempted to characterize breakpoints which precede large rises in dengue case counts. In this paper, Bayesian regime switching (BRS) models were employed to infer epidemic and endemic regimes of dengue transmissions, each containing regime specific processes which drive the growth and decline of dengue cases, estimated using a custom built multi-move Gibbs sampling algorithm. Assessments against various baseline showed that BRS performs better in characterizing dengue transmissions. The dengue regimes estimated by BRS are characterized by their persistent nature. Next, climate analysis showed no short nor long term associations between classified regimes with climate. Lastly, fitting BRS to simulated disease data generated from a mechanistic model, we showed links between disease infectivity and regimes classified using BRS. The model proposed could be applied to other localities and diseases under minimal data requirements where transmission counts over time are collected.

Dengue is an arbovirus affecting global populations. Frequent outbreaks occur, especially in equatorial cities such as Singapore, where year-round tropical climate, large daily influx of travelers and population density provide the ideal conditions for dengue to transmit. Little work has, however, quantified the peaks of dengue outbreaks, when health systems are likely to be most stretched. Nor have methods been developed to infer differences in exogenous factors which lead to the rise and fall of dengue case counts across extreme and non-extreme periods. In this paper, we developed time varying extreme mixture (tvEM) methods to account for the temporal dependence of dengue case counts across extreme and non-extreme periods. This approach permits inference of differences in climatic forcing across non-extreme and extreme periods of dengue case counts, quantification of their temporal dependence as well as estimation of thresholds with associated uncertainties to determine dengue case count extremities. Using tvEM, we found no evidence that weather affects dengue case counts in the near term for non-extreme periods, but that it has non-linear and mixed signals in influencing dengue through tvEM parameters in the extreme periods. Using the most appropriate tvEM specification, we found that a threshold at the 70th (95% credible interval 41.1, 83.8) quantile is optimal, with extreme events of 526.6, 1052.2 and 1183.6 weekly case counts expected at return periods of 5, 50 and 75 years. Weather parameters at a 1% scaled increase was found to decrease the long-run expected case counts, but larger increases would lead to a drastic expected rise from the baseline correspondingly. The tvEM approach can provide valuable inference on the extremes of time series, which in the case of infectious disease notifications, allows public health officials to understand the likely scale of outbreaks in the long run., Author summary Dengue is an arbovirus affecting populations across much of the globe. Frequent outbreaks occur, especially in equatorial cities such as Singapore, where the year-round tropical climate, large daily influx of travelers and population density provide the ideal conditions for dengue transmission. Little work has however quantified the peaks of dengue outbreaks, when health systems are likely to be most stretched. Nor have methods been developed to infer differences in exogenous factors which lead to the rise and fall of dengue case counts across extreme and non extreme periods. In this paper, we developed time varying extreme mixture (tvEM) methods to account for the temporal dependence of dengue case counts across extreme and non-extreme periods. tvEM is able to infer differences in climatic forcing across non-extreme and extreme periods of dengue case counts, their temporal dependence as well as estimate suitable thresholds with associated uncertainties to determine dengue case count extremities. Using tvEM, we found no evidence that weather affects dengue case counts in the near term for non extreme periods, but has non-linear and mixed signals in influencing dengue through tvEM parameters in the extreme periods. Using the most appropriate tvEM specification, we found that a high percentile threshold is estimated, with dengue outbreak events far larger than currently observed to be expected in 5, 50 and 75 years. Weather parameters at a 1% scaled increase was found to decrease the long-run expected case counts, but larger increases would lead to a drastic expected rise from the baseline correspondingly. tvEM can provide valuable inference on the extremes of time series, which in the case of infectious disease data, allows public health officials to understand factors and the likely scale of infectious disease outbreaks in the long run.

During these days of global emergency for the COVID-19 disease outbreak, there is an urgency to share reliable information able to help worldwide life scientists to get better insights and make sense of the large amount of data currently available. In this study we used the results presented in [1] to perform two different Systems Biology analyses on the HCoV-host interactome. In the first one, we reconstructed the interactome of the HCoV-host proteins, integrating it with highly reliable miRNA and drug interactions information. We then added the IL-6 gene, identified in recent publications [2] as heavily involved in the COVID-19 progression and, interestingly, we identified several interactions with the reconstructed interactome. In the second analysis, we performed a Gene Ontology and a Pathways enrichment analysis on the full set of the HCoV-host interactome proteins and on the ones belonging to a significantly dense cluster of interacting proteins identified in the first analysis. Results of the two analyses provide a compact but comprehensive glance on some of the current state-of-the-art regulations, GO, and pathways involved in the HCoV-host interactome, and that could support all scientists currently focusing on SARS-CoV-2 research., Author summary In this paper we provide data about the HCoV-host interactome that can be extracted from the integration of several public available databases. We used the initial interactome published by Zhou et al. and analyzed if there are already known and validated interactions. We also looked into possible known miRNAs and drugs interactions to suggest possible biomarker candidates and treatment options. We also performed a Gene Ontology and a Pathways enrichment analysis to understand which are the pathways most likely involved in the proteins targeted by SARS-CoV-2. This paper not only provides a set of validated and reliable data that could help researchers in their fight against the COVID-19 disease outbreak, but also demonstrates how Systems Biology can be effectively used to quickly gather preliminary but still significant data without resorting only to expensive lab experiments.

The ability to produce timely and accurate flu forecasts in the United States can significantly impact public health. Augmenting forecasts with internet data has shown promise for improving forecast accuracy and timeliness in controlled settings, but results in practice are less convincing, as models augmented with internet data have not consistently outperformed models without internet data. In this paper, we perform a controlled experiment, taking into account data backfill, to improve clarity on the benefits and limitations of augmenting an already good flu forecasting model with internet-based nowcasts. Our results show that a good flu forecasting model can benefit from the augmentation of internet-based nowcasts in practice for all considered public health-relevant forecasting targets. The degree of forecast improvement due to nowcasting, however, is uneven across forecasting targets, with short-term forecasting targets seeing the largest improvements and seasonal targets such as the peak timing and intensity seeing relatively marginal improvements. The uneven forecasting improvements across targets hold even when “perfect” nowcasts are used. These findings suggest that further improvements to flu forecasting, particularly seasonal targets, will need to derive from other, non-nowcasting approaches., Author summary It has been demonstrated in retrospective settings that flu forecasting can be improved by augmenting forecasting models with internet-based nowcasts (i.e., one-week-ahead forecasts generated with internet data). The improvement of internet-assisted forecasting models, however, has not translated to overall improvement in flu forecasting of public health-relevant targets. This is partially due to the relatively simple forecasting models that nowcasts are augmenting and partially because nowcasts do not directly inform all public health-relevant targets, such as the start, the peak timing, and the peak intensity of the flu season (i.e., seasonal targets). This paper conducts an experiment to provide clarity on the benefits and limitations of augmenting flu forecasting models with internet-based nowcasts in practice. We show that 1) nowcasts can improve flu forecasting across all geographic regions, flu seasons, and public health-relevant targets, including seasonal targets, and 2) the benefits of nowcasting are uneven, as even in the perfect nowcasting setting, only marginal improvements to forecasts of seasonal targets are possible relative to short-term forecasts. This is because nowcasts provide direct information about short-term targets but only indirect information about seasonal targets. This paper supports previous findings that nowcasts can improve flu forecasting but clarifies the limitations of those improvements, both in terms of magnitude of possible improvement as well as which targets can be improved. The continued advancement of flu forecasting hinges on the development of model improvements separate from nowcasting.

As science becomes increasingly interdisciplinary, we are expected to acquire both breadth of knowledge and depth of expertise. In bioinformatics, this is especially true. Keeping up to date with major techniques across multiple specialisations can be daunting, but you need not face it alone. A journal club is an excellent way to take in the scientific literature, keep up with developments in your field, and hone your communication and analytical skills. In general, a journal club is a group of people who meet regularly to discuss one or more scientific papers. The structure of such a club can vary. In the more traditional format, an individual studies a paper and then presents it to the group, usually in the form of PowerPoint slides, with time for questions. In some institutions, the journal club is for students only, designed to fulfill the requirements of a course or postgraduate program; attendance is obligatory, the scope of the literature is narrow, and the format is prescribed. The preparation of slides and a lecture may be required. Other kinds of journal clubs are just lab meetings in disguise, with the usual lab head and group members in attendance and one member nominated to present the paper. A formal style often fits well within an established academic structure—but what if your discipline is emerging? Consider the field of bioinformatics. Expertise may be spread across departments and institutions, and there may not be an obvious place or critical mass in any one lab for a traditional journal club. Research students, “pet bioinformaticians,” [1] and those interested in bioinformatics from adjoining fields all need a place to gather. We are pleased to offer an alternative structure to address this situation—an informal journal club, designed to bring together a diversity of backgrounds and career stages to discuss bioinformatics while building a network of like-minded peers. Additional benefits of such a journal club may include friendship and breakfast (see Rule 2)! We thoroughly recommend it to anyone who asks (as well as those who don’t). While this advice is drawn from our experiences in the Parkville Bioinformatics Journal Club, it is applicable to developing informal journal clubs of all disciplines. The advice contained in these rules will also help those who want to spice up their existing formal format. So don’t be a “lonely bioinformatician”[1], create a journal club! Follow these Ten Simple Rules to find out how.

Approximately 85% of tuberculosis (TB) related deaths occur in low- and middle-income countries where health resources are scarce. Effective priority setting is required to maximise the impact of limited budgets. The Optima TB tool has been developed to support analytical capacity and inform evidence-based priority setting processes for TB health benefits package design. This paper outlines the Optima TB framework and how it was applied in Belarus, an upper-middle income country in Eastern Europe with a relatively high burden of TB. Optima TB is a population-based disease transmission model, with programmatic cost functions and an optimisation algorithm. Modelled populations include age-differentiated general populations and higher-risk populations such as people living with HIV. Populations and prospective interventions are defined in consultation with local stakeholders. In partnership with the latter, demographic, epidemiological, programmatic, as well as cost and spending data for these populations and interventions are then collated. An optimisation analysis of TB spending was conducted in Belarus, using program objectives and constraints defined in collaboration with local stakeholders, which included experts, decision makers, funders and organisations involved in service delivery, support and technical assistance. These analyses show that it is possible to improve health impact by redistributing current TB spending in Belarus. Specifically, shifting funding from inpatient- to outpatient-focused care models, and from mass screening to active case finding strategies, could reduce TB prevalence and mortality by up to 45% and 50%, respectively, by 2035. In addition, an optimised allocation of TB spending could lead to a reduction in drug-resistant TB infections by 40% over this period. This would support progress towards national TB targets without additional financial resources. The case study in Belarus demonstrates how reallocations of spending across existing and new interventions could have a substantial impact on TB outcomes. This highlights the potential for Optima TB and similar modelling tools to support evidence-based priority setting., Author summary Tuberculosis (TB) remains a leading global cause of death and morbidity, and 85% of deaths occur in countries where resources for TB care and control are limited. Many countries cannot finance all TB interventions or technologies, which means difficult decisions on what to prioritise and publically finance. Modelling tools can help decision-makers set priorities based on evidence, in a systematic and transparent way. This study presents Optima TB, a tool that estimates which allocations of spending across interventions will most likely maximise specified objectives—such as minimising TB deaths, prevalence and incidence. In partnership with local decision-makers and stakeholders, Optima TB was applied in Belarus. Recommendations from the model findings include focussing investment on outpatient rather than inpatient care and actively finding people with TB (e.g. through contact tracing) rather than mass testing of the population. The recommended reallocations of spending could reduce TB prevalence and deaths by up to 45% and 50%, respectively, by 2035 for the same amount of spending. Key stakeholders were engaged throughout the analysis and findings and uncertainty around the results were clearly communicated with decision-makers. The timeliness of the results helped inform national dialogue on TB care reform, among other key policy discussions.

Increased availability of epidemiological data, novel digital data streams, and the rise of powerful machine learning approaches have generated a surge of research activity on real-time epidemic forecast systems. In this paper, we propose the use of a novel data source, namely retail market data to improve seasonal influenza forecasting. Specifically, we consider supermarket retail data as a proxy signal for influenza, through the identification of sentinel baskets, i.e., products bought together by a population of selected customers. We develop a nowcasting and forecasting framework that provides estimates for influenza incidence in Italy up to 4 weeks ahead. We make use of the Support Vector Regression (SVR) model to produce the predictions of seasonal flu incidence. Our predictions outperform both a baseline autoregressive model and a second baseline based on product purchases. The results show quantitatively the value of incorporating retail market data in forecasting models, acting as a proxy that can be used for the real-time analysis of epidemics., Comment: 17 pages, 2 figures, 4 tables (1 in appendix), 1 algorithm, submitted to PLOS Computational Biology

Neonatal invasive disease caused by Group B Streptococcus (GBS) is responsible for much acute mortality and long-term morbidity. To guide development of better prevention strategies, including maternal vaccines that protect neonates against GBS, it is necessary to estimate the burden of this condition globally and in different regions. Here, we present a Bayesian model that estimates country-specific invasive GBS (iGBS) disease incidence in children aged 0 to 6 days. The model combines different types of epidemiological data, each of which has its own limitations: GBS colonization prevalence in pregnant women, risk of iGBS disease in children born to GBS-colonized mothers and direct estimates of iGBS disease incidence where available. In our analysis, we present country-specific maternal GBS colonization prevalence after adjustment for GBS detection assay used in epidemiological studies. We then integrate these results with other epidemiological data and estimate country-level incidence of iGBS disease including in countries with no studies that directly estimate incidence. We are able to simultaneously estimate two key epidemiological quantities: the country-specific incidence of early-onset iGBS disease, and the risk of iGBS disease in babies born to GBS-colonized women. Overall, we believe our method will contribute to a more comprehensive quantification of the global burden of this disease, inform cost-effectiveness assessments of potential maternal GBS vaccines and identify key areas where data are necessary., Author summary Invasive disease caused by Group B Streptococcus (GBS) in young infants continues to be a major public health problem in both developed and developing countries. However, data on the incidence of this infection during the first week of life are only available for a small number of countries, which has complicated the quantification of the burden of this disease globally. In this paper, we develop a Bayesian framework to estimate the incidence of invasive GBS infection that combines data from multiple types of epidemiological studies, with adjustment for relevant factors such as diagnostic methods used in the studies. We present estimates from a series of models, and our results highlight the potential weaknesses of different types of studies and the importance to consider the entire evidence when estimating global burden of invasive neonatal infections. We believe this model is a step toward better quantification of the number of cases in different regions.

Hosting an artist in a scientific lab is likely a new experience for many scientists in the natural and engineering sciences, and perhaps also for many artists, yet it can be a very beneficial experience for both parties [1]. “Art and science are in a tension that is most fruitful when these disciplines observe and penetrate each other and experience how much of the other they themselves still contain” [2]. During our science and art collaborations in the last years, we have learned what connects and what separates our disciplines, how different yet common our worlds of working and thinking are, and how stimulating such collaborations can be. Although scientists and artists belong to two different cultural worlds, many share research as a congruent method to explore and understand the world around us. Often, scientific and artistic work spaces are indistinguishable as they are full of equipment, materials, tools, and computers to run experiments and analyze data [3,4]. Science and art are fundamentally connected through their focus on creativity [5]. Also, both scientists and artists deliberately venture into the public realm in the spirit of Hannah Arendt: “Humanity is never won in loneliness and never by handing one’s work over to the public. Only if you take your life and person[ality] into the venture of the public realm, will you reach [humanity]” [6]. At the most fundamental level, science and art both try to understand the world around us and to guide society to recognize and solve problems. Artistic and scientific research may also have much more in common than one expects at first sight: They both involve years of schools and personal development, they both involve trial and error, and the sharing of results with different communities. However, transdisciplinary cooperation requires openness, a willingness to take risks, the ability for self-reflection, respect, and esteem for the other culture as well as a lot of appreciative listening from both parties [7,8]. Our paper thus intends to serve as a practical guide for both, artists-in-residence and the hosting scientific lab to easier cross borders, to better collaborate, to better learn from each other, and to sustainably bridge the different cultures of science and the arts. Our discussion starts at the point where a decision for such an interaction has already taken place. Still wondering if this is for you? There is much to gain for both sides. For the scientists, for example, this interaction can be a source of new ideas and questions, offering new points of view. Some of us also felt that this interaction offered training in explaining research in clear, simple language, and provided opportunities for interfacing with the science-curious public in a curated context. For the artists, this can be about learning new tools, methods, and approaches and about the specific topics on which a lab works. Some of the following 10 “rules” apply more to the artist, some more to the hosting science lab, and some to both (Fig 1). Open in a separate window Fig 1 Summary of the 10 rules, arrayed from intellectual/philosophical to practical/logistical and divided into rules more applicable to the hosting science lab and rules relevant for both the hosting lab and the artist. Rule 1: Be open The basic mindset and attitude required for both scientists and artists is openness. Openness to new input, willingness to share ideas, and a sharing attitude. It is not at all required to have an artistic “inclination” on the part of the hosting scientist, but nothing can replace an open attitude. Be open to accept that research can be both: scientific research and artistic research (for a definition of artistic research, see [9]).

Research publications and data nowadays should be publicly available on the internet and, theoretically, usable for everyone to develop further research, products, or services. The long-term accessibility of research data is, therefore, fundamental in the economy of the research production process. However, the availability of data is not sufficient by itself, but also their quality must be verifiable. Measures to ensure reuse and reproducibility need to include the entire research life cycle, from the experimental design to the generation of data, quality control, statistical analysis, interpretation, and validation of the results. Hence, high-quality records, particularly for providing a string of documents for the verifiable origin of data, are essential elements that can act as a certificate for potential users (customers). These records also improve the traceability and transparency of data and processes, therefore, improving the reliability of results. Standards for data acquisition, analysis, and documentation have been fostered in the last decade driven by grassroot initiatives of researchers and organizations such as the Research Data Alliance (RDA). Nevertheless, what is still largely missing in the life science academic research are agreed procedures for complex routine research workflows. Here, well-crafted documentation like standard operating procedures (SOPs) offer clear direction and instructions specifically designed to avoid deviations as an absolute necessity for reproducibility. Therefore, this paper provides a standardized workflow that explains step by step how to write an SOP to be used as a starting point for appropriate research documentation., Zweitver��ffentlichungen der Universit��t Potsdam : Mathematisch-Naturwissenschaftliche Reihe; 1201

This paper presents a data analysis framework to uncover relationships between health conditions, age and sex for a large population of patients. We study a massive heterogeneous sample of 1.7 million patients in Brazil, containing 47 million of health records with detailed medical conditions for visits to medical facilities for a period of 17 months. The findings suggest that medical conditions can be grouped into clusters that share very distinctive densities in the ages of the patients. For each cluster, we further present the ICD-10 chapters within it. Finally, we relate the findings to comorbidity networks, uncovering the relation of the discovered clusters of age densities to comorbidity networks literature., Author summary Age and sex of a patient can be directly related to susceptibilities to certain medical conditions. We present a method to generate clusters of human phenotype, based on the age of the population. This method helps extract knowledge on age and sex from the data. The age and sex correlations with disease conditions can help in a task of predicting the susceptibility of incoming patients to conditions.

Research from educational psychology suggests that teaching and learning are subject-specific activities: learning programming has a different set of challenges and techniques than learning physics or learning to read and write. Computing is a younger discipline than mathematics, physics, or biology, and while there have been correspondingly fewer studies of how best to teach it, there is a growing body of evidence about what works and what doesn’t. This paper presents ten quick tips that should be the foundation of any teaching of programming, whether formal or informal.