How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences.

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MotivationDisruption of protein–protein interactions can mitigate antibody recognition of therapeutic proteins, yield monomeric forms of oligomeric proteins, and elucidate signaling mechanisms, among other applications. While designing affinity-enhancing mutations remains generally quite challenging, both statistically and physically based computational methods can precisely identify affinity-reducing mutations. In order to leverage this ability to design variants of a target protein with disrupted interactions, we developed the DisruPPI protein design method (DISRUpting Protein–Protein Interactions) to optimize combinations of mutations simultaneously for both disruption and stability, so that incorporated disruptive mutations do not inadvertently affect the target protein adversely.ResultsTwo existing methods for predicting mutational effects on binding, FoldX and INT5, were demonstrated to be quite precise in selecting disruptive mutations from the SKEMPI and AB-Bind databases of experimentally determined changes in binding free energy. DisruPPI was implemented to use an INT5-based disruption score integrated with an AMBER-based stability assessment and was applied to disrupt protein interactions in a set of different targets representing diverse applications. In retrospective evaluation with three different case studies, comparison of DisruPPI-designed variants to published experimental data showed that DisruPPI was able to identify more diverse interaction-disrupting and stability-preserving variants more efficiently and effectively than previous approaches. In prospective application to an interaction between enhanced green fluorescent protein (EGFP) and a nanobody, DisruPPI was used to design five EGFP variants, all of which were shown to have significantly reduced nanobody binding while maintaining function and thermostability. This demonstrates that DisruPPI may be readily utilized for effective removal of known epitopes of therapeutically relevant proteins.Availability and implementationDisruPPI is implemented in the EpiSweep package, freely available under an academic use license.Supplementary information Supplementary data are available at Bioinformatics online.

Automated analysis of privacy policies has proved a fruitful research direction, with developments such as automated policy summarization, question answering systems, and compliance detection. Prior research has been limited to analysis of privacy policies from a single point in time or from short spans of time, as researchers did not have access to a large-scale, longitudinal, curated dataset. To address this gap, we developed a crawler that discovers, downloads, and extracts archived privacy policies from the Internet Archive's Wayback Machine. Using the crawler and following a series of validation and quality control steps, we curated a dataset of 1,071,488 English language privacy policies, spanning over two decades and over 130,000 distinct websites.Our analyses of the data paint a troubling picture of the transparency and accessibility of privacy policies. By comparing the occurrence of tracking-related terminology in our dataset to prior web privacy measurements, we find that privacy policies have consistently failed to disclose the presence of common tracking technologies and third parties. We also find that over the last twenty years privacy policies have become even more difficult to read, doubling in length and increasing a full grade in the median reading level. Our data indicate that self-regulation for first-party websites has stagnated, while self-regulation for third parties has increased but is dominated by online advertising trade associations. Finally, we contribute to the literature on privacy regulation by demonstrating the historic impact of the GDPR on privacy policies.