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Abstract Background Histone Mark Modifications (HMs) are crucial actors in gene regulation, as they actively remodel chromatin to modulate transcriptional activity: aberrant combinatorial patterns of HMs have been connected with several diseases, including cancer. HMs are, however, reversible modifications: understanding their role in disease would allow the design of ‘epigenetic drugs’ for specific, non-invasive treatments. Standard statistical techniques were not entirely successful in extracting representative features from raw HM signals over gene locations. On the other hand, deep learning approaches allow for effective automatic feature extraction, but at the expense of model interpretation. Results Here, we propose ShallowChrome, a novel computational pipeline to model transcriptional regulation via HMs in both an accurate and interpretable way. We attain state-of-the-art results on the binary classification of gene transcriptional states over 56 cell-types from the REMC database, largely outperforming recent deep learning approaches. We interpret our models by extracting insightful gene-specific regulative patterns, and we analyse them for the specific case of the PAX5 gene over three differentiated blood cell lines. Finally, we compare the patterns we obtained with the characteristic emission patterns of ChromHMM, and show that ShallowChrome is able to coherently rank groups of chromatin states w.r.t. their transcriptional activity. Conclusions In this work we demonstrate that it is possible to model HM-modulated gene expression regulation in a highly accurate, yet interpretable way. Our feature extraction algorithm leverages on data downstream the identification of enriched regions to retrieve gene-wise, statistically significant and dynamically located features for each HM. These features are highly predictive of gene transcriptional state, and allow for accurate modeling by computationally efficient logistic regression models. These models allow a direct inspection and a rigorous interpretation, helping to formulate quantifiable hypotheses.

Abstract An increasing number of research programs seek to support adaptation to climate change through the engagement of large‐scale transdisciplinary networks that span countries and continents. While transdisciplinary research processes have been a topic of reflection, practice, and refinement for some time, these trends now mean that the global change research community needs to reflect and learn how to pursue collaborative research on a large scale. This paper shares insights from a seven‐year climate change adaptation research program that supports collaboration between more than 450 researchers and practitioners across four consortia and 17 countries. The experience confirms the importance of attention to careful design for transdisciplinary collaboration, but also highlights that this alone is not enough. The success of well‐designed transdisciplinary research processes is also strongly influenced by relational and systemic features of collaborative relationships. Relational features include interpersonal trust, mutual respect, and leadership styles, while systemic features include legal partnership agreements, power asymmetries between partners, and institutional values and cultures. In the new arena of large‐scale collaborative science efforts, enablers of transdisciplinary collaboration include dedicated project coordinators, leaders at multiple levels, and the availability of small amounts of flexible funds to enable nimble responses to opportunities and unexpected collaborations.