Main

Improving technology allows neurophysiologists to record ever larger datasets. The need for technologies to organize and share these data is growing as scientists begin to assemble into large, international teams. The International Brain Laboratory (IBL) is a collaboration studying the computations supporting decision-making in the mouse1. We have developed modular data-management tools that enable individual laboratories and collaborations to manage experimental subject colonies and track subject- and experiment-level metadata; integrate data from multiple laboratories in a central store for sharing inside or outside the collaboration; access shared data through a programmatic interface; and process incoming data through pipelines that automatically populate a website.

Current neurophysiological datasets comprise multiple recordings from multiple subjects, recorded using diverse devices. These data must be preprocessed, time-aligned and integrated with data such as locations of recording electrodes before they can be used to draw scientific conclusions2,3,4,5,6,7,8. Distributed collaborations pose distinct challenges: while public data release must wait for careful quality control, scientists within the collaboration require immediate access to specific data. This store must be searchable and allow downloading and also revision of individual items, because preprocessing and quality control methods are still evolving9,10,11.

We addressed these problems with an architecture consisting of four modules (Fig. 1). The first module is a web interface for colony management and electronic laboratory notebook that links files arising from each experiment to relevant metadata. The second module integrates data from multiple laboratories into a central database and bulk data store, providing immediate access while allowing updates of individual items. The third automatically runs analyses on newly arrived data, providing results via a web interface. The fourth allows standardization, access and sharing of the data. Full documentation can be found at https://docs.internationalbrainlab.org/ and through links at https://www.internationalbrainlab.com/tools.

To manage data within each laboratory, we developed Alyx, a relational database that links colony management, metadata and laboratory notes to experimental data files. A web graphical user interface allows users to enter metadata as it arrives (such as birth, weaning, genotyping, surgeries or experiments), and a REST application programming interface (API) allows experiment control software to automatically enter metadata. Bulk data files are stored on a laboratory server and linked to experiment and subject metadata in the Alyx database. This tool can be used by single laboratories as well as collaborations: it was developed in one member laboratory before IBL’s founding, and is now used by several laboratories worldwide for non-IBL work. A link to an Alyx user guide can be found via our main documentation page (https://docs.internationalbrainlab.org).

Integrating data between laboratories raises challenges of size and complexity. Large-scale electrophysiology produces hundreds of gigabytes per experiment, for which we have designed a threefold lossless compression algorithm (https://github.com/int-brain-lab/mtscomp) (Supplementary Note 1). A single IBL experiment generates over 150 raw and processed data files. We have devised conventions for organizing and naming these files, termed the Open Neurophysiology Environment (ONE) (Supplementary Note 2; https://one.internationalbrainlab.org), which formalizes how to encode cross-references between files, time synchronization and versioning, and allows local and remote access via an API. ONE provides a way to standardize and share data from individual laboratories, by specifying standard filenames for common data types (Supplementary Note 3) and defining conventions for naming laboratory-specific data files (https://github.com/int-brain-lab/ONE/blob/main/docs/Open_Neurophysiology_Environment_Filename_Convention.pdf). Files from several laboratories are integrated by uploading nightly from laboratory servers to a central server using Globus Online12, coordinated by a central Alyx database that also stores metadata from all laboratories.

Neurophysiology data require preprocessing, such as spike sorting and video analysis. We developed a task management system that uses computers in member laboratories as a processing pool. Computers query the Alyx database for a list of outstanding preprocessing tasks, determined by a dependency graph. Because Alyx is accessed through http, this works despite different universities’ diverse firewall policies, and allows monitoring, logging and restarting all preprocessing tasks. Higher-level analyses are automatically run on newly preprocessed data using DataJoint13, which runs automated analyses and places the results on a website, including summaries of behavioral performance, allowing scientists to monitor training progress, and basic analyses of spike trains. While manual curation of the full dataset will be required before public release, an illustrative curated subset of these data is available on a public website (https://data.internationalbrainlab.org).

To access data, an API allows users to search experiments and load data from the ONE files directly into Python (Supplementary Note 3). This API allows both collaborations and individual laboratories to share data using the same standard. A large collaboration can host files on a server such as Amazon Web Services, and run an Alyx server that allows users to rapidly search and selectively download the data. Individual laboratories can release data compatible with the same API by ‘uploading and forgetting’ a zip of ONE files to a site such as FigShare, for users to download (instructions at https://github.com/int-brain-lab/ONE/blob/main/docs/Open_Neurophysiology_Environment_Filename_Convention.pdf). Users can also access data via Neurodata Without Borders13,14 using software that translates from the ONE standard (https://github.com/catalystneuro/IBL-to-nwb; Supplementary Table 1), or through DataJoint15. A comparison of these and other sharing systems is in Supplementary Note 4. The analyses in a recently published paper1 were made using this system, and an additional example is provided below for evaluating training time.

The IBL architecture was designed for our large-scale collaboration, but its modular design allows components to be used by individual laboratories and smaller-scale collaborations. The Alyx system provides easy-to-use colony management and electronic laboratory notebook features for laboratories or collaborations, linking experimental files to this metadata. The ONE conventions allow data to be organized within a laboratory and shared externally, using standards that scale to large collaborations. Larger collaborations can also benefit from other features such as the automated analyses for web display. We hope that these tools, and additional software we have provided (Supplementary Table 1), will help pave the way forward to an era in which data from neurophysiology laboratories are integrated and shared on a routine basis.

To demonstrate how this system can manage data and metadata, integrate them across laboratories and analyze the results, we evaluated the importance of multiple variables for predicting the time required for mice to complete behavioral training.

Mice were on a visual discrimination task using the standard IBL training pipeline1. Training was considered complete when performance met criteria for the fraction of correct responses, number of completed trials and fitted psychometric parameters, for three consecutive sessions. Behavior on reaching this criterion was similar across mice, but the training time required for mice to meet these criteria was variable, ranging from 5 to 57 training sessions (Fig. 2a). We used the data architecture described above to investigate which factors might predict this variability. Because comprehensive data and metadata from all laboratories were integrated in a centralized and standardized manner, we could quickly perform these analyses.

We investigated whether training time could be predicted from several classes of variables. The first class was subject features: the sex of the animal, the age, weight and weight loss (relative to prewater-restriction weight) on training start. The second was rig ambient measures: temperature, relative humidity and air pressure, averaged across all training sessions. Third, some institute-specific experimental conditions such as the type of light cycle mice were housed in, the protein content of the homecage food and the weekend water regime in place (water restriction versus 2% free homecage citric acid water16). Fourth, metrics assessed from early training sessions including: task performance; median reaction time; total number of trials on the first training session; the changes in those values over the first five training sessions; the total sum of trials performed over the first five training sessions; the variance in the sign of the daily performance change across the first five training sessions; the number of wheel movements per second and the average wheel displacement bias (averaged across the first five training sessions).

A random forest classifier accurately predicted time to reach the performance criterion for each mouse from this feature set (Fig. 2a). Time to criterion was grouped into quartiles and classification accuracy was evaluated by tenfold cross-validation, producing a confusion matrix comparing the predicted and actual quartile for each mouse (Fig. 2b), summarized by an F1 score (Fig. 2c). When trained with all available features, the classifier predicted the true quartile more often than any other (Fig. 2b), with accuracy around two times higher than when trained after randomly shuffling quartile labels (Fig. 2c).

To investigate the importance of each feature, we performed a permutation test on each of the features. The importance of each feature was assessed by the decrease in the classifier’s accuracy after randomly shuffling that feature’s values across all mice. This revealed that one predictor variable was more important than all others: the task performance change across the first five training sessions (Fig. 2d): that is, the percentage correct achieved on session five minus the percentage correctly achieved on session 1. Site-specific features that are hard to standardize across locations, such as food protein content and humidity, were not important to the classifier’s accuracy. The only predictive feature not related to task performance in early days was age.

Given the importance of the 5-day performance change feature compared to the remaining ones, we further evaluated the accuracy of a classifier trained only with this one feature (Fig. 2c). Prediction using only this feature was nearly as accurate as the full classifier, although including other predictor variables resulted in a 14% increase in accuracy.

This large-scale analysis was made possible by the ease and speed of accessing large amounts of behavioral data saved in a standard manner. The obtained results showed that tracking changes in performance during the first few training days was enough to predict training time above chance level, with even better accuracy achieved when also considering other behavioral metrics. The ability to predict final training time after only five training sessions could allow automated decisions about when to drop a subject from the training pipeline.

Methods

The experimental methods used to collect the data analyzed in this paper are described in ref. 1.

For the analysis described in this paper, we accessed the behavioral data using the public DataJoint protocol. Mice selected for the analysis consisted of all mice trained according to the standard IBL training pipeline, up until 23 March 2020. Mice were excluded from the analyses if they were dropped from the pipeline before reaching the end of training. Training was considered complete when performance met criteria for the fraction of correct responses, number of completed trials and fitted psychometric parameters, for three consecutive sessions1.

A random forest classifier was used to assess whether training time could be predicted from several classes of variables: subject features, rig ambient measures, institute-specific experimental conditions and performance metrics from early training sessions. For that, data were processed and organized as a design matrix with shape number of mice × number of variables. For each mouse, we included the following variables: (1) sex; (2) age at the start of training; (3) weight at the start of training; (4) weight loss at the start of training, calculated as the weight fraction relative to the prewater-restriction weight; (5) whether the mouse was housed on an inverted or noninverted light cycle scheme; (6) the percentage of protein content of the homecage food; (7) weekend water regime in place: whether mice were on a traditional water restriction regime or on had free access to 2% free homecage citric acid water16; (8) the training rig temperature, averaged across the first five training sessions; (9) the training rig relative humidity, averaged across the first five training sessions; (10) the training rig air pressure, averaged across the first five training sessions; (11) the fraction of correct responses on the first training session; (12) median reaction time on the first training session; (13) total number of trials on the first training session; (14) difference in fraction of correct responses between first and fifth training sessions; (15) difference in the median reaction time between the first and fifth training sessions; (16) difference in the total number of trials between the first and fifth training sessions; (17) total number of trials performed over the first five training sessions; (18) the variance in the sign of the daily performance change across the first five training sessions (daily performance change was computed as the difference in the fraction of correct responses across consecutive sessions); (19) the amount of wheel movement per second averaged across the first five training sessions and (20) the wheel displacement bias averaged across the first five training sessions (wheel displacement bias was calculated as the amount of wheel displacement divided by the total amount of wheel movement). Missing data that prevented the calculation of any of the above metrics led to the exclusion of the corresponding mouse from the analyses. The predicted variable was the training-time quartile of the mouse. Training time was calculated as the number of training sessions until training completion. The quartiles of the distribution were calculated after exclusion of mice with missing data.

To assess whether training time could be predicted from the listed variables, a random forest classifier was trained on the data, using tenfold cross-validation. For that, scikit-learn functions RanfomForestClassifier and KFold were used. Prediction accuracy of the classifier was computed using the F1-score function. The F1 score reaches 1 for the highest accuracy value and 0 for the worst. It is calculated according to the following formula:

$$F_1 = \frac{{2 \times {\mathrm{true}}\,{\mathrm{positives}}}}{{2 \times {\mathrm{true}}\,{\mathrm{positives}} + {\mathrm{false}}\,{\mathrm{positives}} + {\mathrm{false}}\,{\mathrm{negatives}}}}$$

Classifier performance was compared with that of a classifier trained on a control dataset in which quartile labels were randomly shuffled (n = 100 shuffles).

To investigate the importance of each feature to the classifier’s performance, we performed a permutation test on each of the features. The importance of each feature was assessed by the decrease in the classifier’s accuracy (F1 score) after randomly shuffling that feature’s values across mice (n = 10 repetitions).

Finally, we further evaluated the accuracy of a classifier trained only on the most important feature, as concluded from the permutation test: the difference in fraction of correct responses between first and fifth training sessions.

Reporting summary

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.