Open Science 2.0: Towards a truly collaborative research ecosystem.

Conversations about open science have reached the mainstream, yet many open science practices such as data sharing remain uncommon. Our efforts towards openness therefore need to increase in scale and aim for a more ambitious target. We need an ecosystem not only where research outputs are openly shared but also in which transparency permeates the research process from the start and lends itself to more rigorous and collaborative research. To support this vision, this Essay provides an overview of a selection of open science initiatives from the past 2 decades, focusing on methods transparency, scholarly communication, team science, and research culture, and speculates about what the future of open science could look like. It then draws on these examples to provide recommendations for how funders, institutions, journals, regulators, and other stakeholders can create an environment that is ripe for improvement.

Improving transparency and scientific rigor in academic publishing.

Progress in basic and clinical research is slowed when researchers fail to provide a complete and accurate report of how a study was designed, executed, and the results analyzed. Publishing rigorous scientific research involves a full description of the methods, materials, procedures, and outcomes. Investigators may fail to provide a complete description of how their study was designed and executed because they may not know how to accurately report the information or the mechanisms are not in place to facilitate transparent reporting. Here, we provide an overview of how authors can write manuscripts in a transparent and thorough manner. We introduce a set of reporting criteria that can be used for publishing, including recommendations on reporting the experimental design and statistical approaches. We also discuss how to accurately visualize the results and provide recommendations for peer reviewers to enhance rigor and transparency. Incorporating transparency practices into research manuscripts will significantly improve the reproducibility of the results by independent laboratories.

Opinion: Independent third-party entities as a model for validation of commercial antibodies.

A vast array of commercial antibodies covers a large percentage of human gene products, but determining which among them is most appropriate for any given application is challenging. This leads to use of non-specific antibodies that contributes to issues with reproducibility. It is our opinion that the community of scientists who use commercial antibodies in their biomedical research would benefit from third-party antibody characterization entities that use standardized operating procedures to assess and compare antibody performance. Ideally, such entities would follow the principles of open science, such that all antibodies against any given protein target would be tested in parallel, and all data generated released to the public domain without bias. Furthermore, there should be no financial incentive for the entity beyond cost-recovery. Such non-profit organizations, combined with other scientific efforts, could catalyse new discoveries by providing scientists with better validated antibody tools.

Incidences of problematic cell lines are lower in papers that use RRIDs to identify cell lines.

The use of misidentified and contaminated cell lines continues to be a problem in biomedical research. Research Resource Identifiers (RRIDs) should reduce the prevalence of misidentified and contaminated cell lines in the literature by alerting researchers to cell lines that are on the list of problematic cell lines, which is maintained by the International Cell Line Authentication Committee (ICLAC) and the Cellosaurus database. To test this assertion, we text-mined the methods sections of about two million papers in PubMed Central, identifying 305,161 unique cell-line names in 150,459 articles. We estimate that 8.6% of these cell lines were on the list of problematic cell lines, whereas only 3.3% of the cell lines in the 634 papers that included RRIDs were on the problematic list. This suggests that the use of RRIDs is associated with a lower reported use of problematic cell lines.

Improving transparency and scientific rigor in academic publishing.

Progress in basic and clinical research is slowed when researchers fail to provide a complete and accurate report of how a study was designed, executed, and the results analyzed. Publishing rigorous scientific research involves a full description of the methods, materials, procedures, and outcomes. Investigators may fail to provide a complete description of how their study was designed and executed because they may not know how to accurately report the information or the mechanisms are not in place to facilitate transparent reporting. Here, we provide an overview of how authors can write manuscripts in a transparent and thorough manner. We introduce a set of reporting criteria that can be used for publishing, including recommendations on reporting the experimental design and statistical approaches. We also discuss how to accurately visualize the results and provide recommendations for peer reviewers to enhance rigor and transparency. Incorporating transparency practices into research manuscripts will significantly improve the reproducibility of the results by independent laboratories.

Improving transparency and scientific rigor in academic publishing.

Progress in basic and clinical research is slowed when researchers fail to provide a complete and accurate report of how a study was designed, executed, and the results analyzed. Publishing rigorous scientific research involves a full description of the methods, materials, procedures, and outcomes. Investigators may fail to provide a complete description of how their study was designed and executed because they may not know how to accurately report the information or the mechanisms are not in place to facilitate transparent reporting. Here, we provide an overview of how authors can write manuscripts in a transparent and thorough manner. We introduce a set of reporting criteria that can be used for publishing, including recommendations on reporting the experimental design and statistical approaches. We also discuss how to accurately visualize the results and provide recommendations for peer reviewers to enhance rigor and transparency. Incorporating transparency practices into research manuscripts will significantly improve the reproducibility of the results by independent laboratories. SIGNIFICANCE: Failure to replicate research findings often arises from errors in the experimental design and statistical approaches. By providing a full account of the experimental design, procedures, and statistical approaches, researchers can address the reproducibility crisis and improve the sustainability of research outcomes. In this piece, we discuss the key issues leading to irreproducibility and provide general approaches to improving transparency and rigor in reporting, which could assist in making research more reproducible.

RRIDs: A Simple Step toward Improving Reproducibility through Rigor and Transparency of Experimental Methods.

With the call for more rigorous scientific reporting, authentication, and transparency from the scientific community and funding agencies, one critical step is to make finding and identifying key resources in the published literature tractable. We discuss here the use of Research Resource Identifiers (RRIDs) as one tool to help resolve this tricky problem in reproducibility.

Resource Disambiguator for the Web: Extracting Biomedical Resources and Their Citations from the Scientific Literature.

The NIF Registry developed and maintained by the Neuroscience Information Framework is a cooperative project aimed at cataloging research resources, e.g., software tools, databases and tissue banks, funded largely by governments and available as tools to research scientists. Although originally conceived for neuroscience, the NIF Registry has over the years broadened in the scope to include research resources of general relevance to biomedical research. The current number of research resources listed by the Registry numbers over 13K. The broadening in scope to biomedical science led us to re-christen the NIF Registry platform as SciCrunch. The NIF/SciCrunch Registry has been cataloging the resource landscape since 2006; as such, it serves as a valuable dataset for tracking the breadth, fate and utilization of these resources. Our experience shows research resources like databases are dynamic objects, that can change location and scope over time. Although each record is entered manually and human-curated, the current size of the registry requires tools that can aid in curation efforts to keep content up to date, including when and where such resources are used. To address this challenge, we have developed an open source tool suite, collectively termed RDW: Resource Disambiguator for the (Web). RDW is designed to help in the upkeep and curation of the registry as well as in enhancing the content of the registry by automated extraction of resource candidates from the literature. The RDW toolkit includes a URL extractor from papers, resource candidate screen, resource URL change tracker, resource content change tracker. Curators access these tools via a web based user interface. Several strategies are used to optimize these tools, including supervised and unsupervised learning algorithms as well as statistical text analysis. The complete tool suite is used to enhance and maintain the resource registry as well as track the usage of individual resources through an innovative literature citation index honed for research resources. Here we present an overview of the Registry and show how the RDW tools are used in curation and usage tracking.

Big data from small data: data-sharing in the 'long tail' of neuroscience.

The launch of the US BRAIN and European Human Brain Projects coincides with growing international efforts toward transparency and increased access to publicly funded research in the neurosciences. The need for data-sharing standards and neuroinformatics infrastructure is more pressing than ever. However, 'big science' efforts are not the only drivers of data-sharing needs, as neuroscientists across the full spectrum of research grapple with the overwhelming volume of data being generated daily and a scientific environment that is increasingly focused on collaboration. In this commentary, we consider the issue of sharing of the richly diverse and heterogeneous small data sets produced by individual neuroscientists, so-called long-tail data. We consider the utility of these data, the diversity of repositories and options available for sharing such data, and emerging best practices. We provide use cases in which aggregating and mining diverse long-tail data convert numerous small data sources into big data for improved knowledge about neuroscience-related disorders.

OMICtools: an informative directory for multi-omic data analysis.

Recent advances in 'omic' technologies have created unprecedented opportunities for biological research, but current software and database resources are extremely fragmented. OMICtools is a manually curated metadatabase that provides an overview of more than 4400 web-accessible tools related to genomics, transcriptomics, proteomics and metabolomics. All tools have been classified by omic technologies (next-generation sequencing, microarray, mass spectrometry and nuclear magnetic resonance) associated with published evaluations of tool performance. Information about each tool is derived either from a diverse set of developers, the scientific literature or from spontaneous submissions. OMICtools is expected to serve as a useful didactic resource not only for bioinformaticians but also for experimental researchers and clinicians. Database URL: http://omictools.com/.

Extending the NIF DISCO framework to automate complex workflow: coordinating the harvest and integration of data from diverse neuroscience information resources.

This paper describes how DISCO, the data aggregator that supports the Neuroscience Information Framework (NIF), has been extended to play a central role in automating the complex workflow required to support and coordinate the NIF's data integration capabilities. The NIF is an NIH Neuroscience Blueprint initiative designed to help researchers access the wealth of data related to the neurosciences available via the Internet. A central component is the NIF Federation, a searchable database that currently contains data from 231 data and information resources regularly harvested, updated, and warehoused in the DISCO system. In the past several years, DISCO has greatly extended its functionality and has evolved to play a central role in automating the complex, ongoing process of harvesting, validating, integrating, and displaying neuroscience data from a growing set of participating resources. This paper provides an overview of DISCO's current capabilities and discusses a number of the challenges and future directions related to the process of coordinating the integration of neuroscience data within the NIF Federation.

Modulation of epileptiform activity by glutamine and system A transport in a model of post-traumatic epilepsy.

Epileptic activity arises from an imbalance in excitatory and inhibitory synaptic transmission. To determine if alterations in the metabolism of glutamate, the primary excitatory neurotransmitter, might contribute to epilepsy we directly and indirectly modified levels of glutamine, an immediate precursor of synaptically released glutamate, in the rat neocortical undercut model of hyperexcitability and epilepsy. We show that slices from injured cortex take up glutamine more readily than control slices, and an increased expression of the system A transporters SNAT1 and SNAT2 likely underlies this difference. We also examined the effect of exogenous glutamine on evoked and spontaneous activity and found that addition of physiological concentrations of glutamine to perfusate of slices isolated from injured cortex increased the incidence and decreased the refractory period of epileptiform potentials. By contrast, exogenous glutamine increased the amplitude of evoked potentials in normal cortex, but did not induce epileptiform potentials. Addition of physiological concentrations of glutamine to perfusate of slices isolated from injured cortex greatly increased abnormal spontaneous activity in the form of events resembling spreading depression, again while having no effect on slices from normal cortex. Interestingly, similar spreading depression like events were noted in control slices at supraphysiological levels of glutamine. In the undercut cortex addition of methylaminoisobutyric acid (MeAIB), an inhibitor of the system A glutamine transporters attenuated all physiological effects of added glutamine suggesting that uptake through these transporters is required for the effect of glutamine. Our findings support a role for glutamine transport through SNAT1 and/or SNAT2 in the maintenance of abnormal activity in this in vitro model of epileptogenesis and suggest that system A transport and glutamine metabolism are potential targets for pharmacological intervention in seizures and epilepsy.

Cortical injury affects short-term plasticity of evoked excitatory synaptic currents.

The hypothesis that plastic changes in the efficacy of excitatory neurotransmission occur in areas of chronic cortical injury was tested by assessing short-term plasticity of evoked excitatory synaptic currents (EPSCs) in neurons of partially isolated neocortical islands (undercut cortex). Whole cell recordings were obtained from layer V pyramidal neurons of sensorimotor cortical slices prepared from P36-P43 control and undercut rats. AMPA/kainate receptor-mediated EPSCs elicited by stimuli delivered at 40 to 66.7 Hz exhibited more paired-pulse depression (PPD) in undercut cortex than control, the time constant of depression evoked by trains of 20- to 66.7-Hz stimuli was faster, and the steady-state amplitude of EPSCs reached after five to seven EPSCs was lower. An antagonist of the glutamate autoreceptor, group II mGluR, increased the steady-state amplitude of EPSCs from undercut but not control cortex, suggesting that activation of presynaptic receptors by released glutamate is more prominent in undercut cortex. In contrast, the GABA(B) receptor antagonist (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl)phosphinic acid had no effect. Increasing [Ca(2+)](o) from 2 to 4 mM increased PPD, with a smaller effect in neurons of the undercut. The I-V relationship of AMPA/kainate receptor-mediated EPSCs was close to linear in both control and undercut neurons, and spermine had no significant effect on the EPSCs, suggesting that decreases in postsynaptic glutamate receptors containing the GluR2 subunit were not involved in the alterations in short-term plasticity. Results are compatible with an increase in the probability of transmitter release at excitatory synapses in undercut cortex due to functional changes in presynaptic terminals.