Sperm capacitation is a post-testicular maturation step endowing spermatozoa with fertilizing capacity within the female reproductive tract, significant for fertility, reproductive health, and contraception. Recently discovered mammalian sperm zinc signatures and their changes during sperm in vitro capacitation (IVC) warranted a more in-depth study of zinc interacting proteins (further zincoproteins). Here, we identified 1752 zincoproteins, with 102 changing significantly in abundance (P < 0.05) after IVC. These are distributed across 8 molecular functions, 16 biological processes, and 22 protein classes representing 130 pathways. Two key, paradigm-shifting observations were made: i) during sperm capacitation, molecular functions of zincoproteins are both upregulated and downregulated within several molecular function categories; and ii) Huntington’s and Parkinson’s disease pathways were the two most represented, making spermatozoon a candidate model for studying neurodegenerative diseases. These findings highlight the importance of Zn²⁺homeostasis in reproduction, offering new avenues in semen processing for human-assisted reproductive therapy, identification of somatic-reproductive comorbidities, and livestock breeding.

Interactions between proteins and ions are essential for various biological functions like structural stability, metabolism, and signal transport. Given that more than half of all proteins bind to ions, it is becoming crucial to identify ion-binding sites. The accurate identification of protein–ion binding sites helps us to understand proteins’ biological functions and plays a significant role in drug discovery. While several computational approaches have been proposed, this remains a challenging problem due to the small size and high versatility of metals and acid radicals. In this study, we propose IonPred, a sequence-based approach that employs ELECTRA (Efficiently Learning an Encoder that Classifies Token Replacements Accurately) to predict ion-binding sites using only raw protein sequences. We successfully fine-tuned our pretrained model to predict the binding sites for nine metal ions (Zn²⁺, Cu²⁺, Fe²⁺, Fe³⁺, Ca²⁺, Mg²⁺, Mn²⁺, Na⁺, and K⁺) and four acid radical ion ligands (CO₃²⁻, SO₄²⁻, PO₄³⁻, NO₂⁻). IonPred surpassed six current state-of-the-art tools by over 44.65% and 28.46%, respectively, in the F1 score and MCC when compared on an independent test dataset. Our method is more computationally efficient than existing tools, producing prediction results for a hundred sequences for a specific ion in under ten minutes.

Objective The evaluation of natural language processing (NLP) models for clinical text de-identification relies on the availability of clinical notes, which is often restricted due to privacy concerns. The NLP Sandbox is an approach for alleviating the lack of data and evaluation frameworks for NLP models by adopting a federated, model-to-data approach. This enables unbiased federated model evaluation without the need for sharing sensitive data from multiple institutions. Materials and Methods We leveraged the Synapse collaborative framework, containerization software, and OpenAPI generator to build the NLP Sandbox (nlpsandbox.io). We evaluated two state-of-the-art NLP de-identification focused annotation models, Philter and NeuroNER, using data from three institutions. We further validated model performance using data from an external validation site. Results We demonstrated the usefulness of the NLP Sandbox through de-identification clinical model evaluation. The external developer was able to incorporate their model into the NLP Sandbox template and provide user experience feedback. Discussion We demonstrated the feasibility of using the NLP Sandbox to conduct a multi-site evaluation of clinical text de-identification models without the sharing of data. Standardized model and data schemas enable smooth model transfer and implementation. To generalize the NLP Sandbox, work is required on the part of data owners and model developers to develop suitable and standardized schemas and to adapt their data or model to fit the schemas. Conclusions The NLP Sandbox lowers the barrier to utilizing clinical data for NLP model evaluation and facilitates federated, multi-site, unbiased evaluation of NLP models.

Interactions between proteins and ions are essential for various biological functions like structural stability, metabolism, and signal transport. Given that more than half of all proteins bind to ions, it becomes crucial to identify ion-binding sites. Accurate identification of protein-ion binding sites helps us to understand proteins’ biological functions and plays a significant role in drug discovery. While several computational approaches have been proposed, this remains a challenging problem due to the small size and high versatility of metals and acid radicals. In this study, we propose IonPred, a sequence-based approach that employs ELECTRA (Efficiently Learning an Encoder that Classifies Token Replacements Accurately) to predict ion binding sites using only raw protein sequences. We successfully fine-tuned our pretrained model to predict the binding sites for nine metal ions (Zn2+, Cu2+, Fe2+, Fe3+, Ca2+, Mg2+, Mn2+, Na+, and K+) and four acid radical ion ligands (CO32−, SO42−, PO43−, NO2−). IonPred surpassed six current state-of-the-art tools by over 44.65% and 28.46% respectively in F1 score and MCC when compared on an independent test dataset. Our method is more computationally efficient than existing tools producing prediction results for a hundred sequences for a specific ion in under ten minutes.