ABSTRACT Discovery in biological sciences has shifted to increasingly rely on high throughput multi-omic data. The advent of single cell (sc) transcriptomics further revolutionized research in our field, given the intricate structure of the inner ear organs consisting of numerous distinct cell types that function in concert to properly sense hearing and balance. Harnessing the wealth of existing and future multi-omic, multi-modality and multi-species data is challenged by their ever-increasing data size and relative inaccessibility to biologists that are not trained in bioinformatics. The gEAR, gene Expression Analysis Resources (umgear.org), is a cloud-based `one-stop- shop' where inner ear-related multi-omic data can be explored and analyzed by biologists without requiring programming skills. Over the past five years, the gEAR has become a critically valuable resource to our field. The impact of the gEAR on the field is reflected by its 846 registered users, 440 datasets (over 70 organized in thematic profiles in the public domain), and thousands of monthly visits. The goal of this proposal is to implement necessary improvements in the gEAR that will significantly enhance the ability of researchers to infer biological insights from the omics data generated by their own laboratories and from omics datasets in the public domain. We will: (1) continuously upload and curate ear- related multi-omic data from contributing laboratories and the public domain; (2) construct an integrated epigenetic and transcriptomic atlas of the developing and mature mouse cochlea (a) as a necessary scaffold for cross dataset integration, and (b) as necessary data for bridging the gap between gene expression and gene regulation; (3) implement advanced bioinformatic analytical tools in the gEAR; (4) enhance the user- interface; (5) make scalability, performance and stability improvements; (6) integrate the gEAR with analytical notebooks to allow more complex analyses with minimal training; and (7) continue our education and outreach efforts. In addition to user-surveys, we will establish both user and technology expertise advisory boards to provide feedback and guide development. Diverse expertise is required for the efficient operation and development of the gEAR bioinformatics platform. Our multi-disciplinary team members are a surgeon-scientist (PI), bioinformaticians (Co-Is), biologists and engineers. Our experience in turning the gEAR from an abstract idea to a successful platform, widely adapted in the ear field, and with multiple successful clones including NeMO Analytics (nemoanalytics.org) for the BRAIN initiative should attest to our experience, expertise, and ability to deliver. Completion of the proposed gEAR advancements will boost fulfillment of the great promises expected from omics data generation and analyses and foster reuse of existing data, thereby catalyzing both basic science discovery and advance development and translation of therapeutics for hearing and balance disorders.

PROJECT NARRATIVE The gene Expression Analysis Resource (gEAR portal, umgear.org) is a cloud-based tool for analysis, visualization and sharing of multi-species multi-omic inner-ear related data. It serves to bridge the gap between the breadth, depth and complexity of high throughput multi-modality omics data and the biologists, which are often not trained in programming, yet require meaningful and rapid access to these data for their work. Completion of the proposed gEAR advancements will catalyze basic science discovery and advance development of therapeutics for hearing and balance disorders.