Patrick Masterson

Reference sequences and annotations serve as the foundation for many lines of research today, from organism and sequence identification to providing a core description of the genes, transcripts and proteins found in an organism's genome. Interpretation of data including transcriptomics, proteomics, sequence variation and comparative analyses based on reference gene annotations informs our understanding of gene function and possible disease mechanisms, leading to new biomedical discoveries. The Reference Sequence (RefSeq) resource created at the National Center for Biotechnology Information (NCBI) leverages both automatic processes and expert curation to create a robust set of reference sequences of genomic, transcript and protein data spanning the tree of life. RefSeq continues to refine its annotation and quality control processes and utilize better quality genomes resulting from advances in sequencing technologies as well as RNA-Seq data to produce high-quality annotated genomes, ortholog predictions across more organisms and other products that are easily accessible through multiple NCBI resources. This report summarizes the current status of the eukaryotic, prokaryotic and viral RefSeq resources, with a focus on eukaryotic annotation, the increase in taxonomic representation and the effect it will have on comparative genomics. The RefSeq resource is publicly accessible at https://www.ncbi.nlm.nih.gov/refseq.

The article considers a particular case of Richard Kearney's characteristic hermeneutical exploration of `the possible' as an `imaginative' way of casting light upon philosophical issues. This particular case is his recent hermeneutical and phenomenological consideration of `Otherness' in the context of philosophy of religion. This consideration, strongly influenced by philosophers such as Heidegger, Levinas, Ricoeur and Derrida, is developed in two of his recent works Strangers, Gods and Monsters and The God Who May Be. The article examines how he seeks to navigate an interpretation of divine otherness as an ethical appeal which escapes the dilemma of a God either so transcendent as to be anonymous or so immanent as to be a mere projection. It outlines how, rejecting onto-theology in favour of eschatology, Kearney envisages the divine as an ethically enabling possibility. This possibility, he claims, enables us to achieve, beyond our own intrinsic resources, an ethical order of justice and love through which the kingdom of God — the God Who May Be — is accomplished. There is a co-relativity between the divine as enabling possibility and humanity which accomplishes this possibility. It investigates the way in which Kearney seeks to legitimize, within a phenomenological frame of reference, an experiential affirmation of this conception of divine transcendence as eschatological possibility. It argues that this phenomenological consideration needs to be qualified and complemented by certain metaphysical considerations which Kearney disputes.

Orthologs are fundamental for enabling comparative genomics analyses that further our understanding of eukaryotic biology. The unprecedented increase in the availability of high-quality eukaryotic genomes necessitates scalable and accurate methods for orthology inference. The National Center for Biotechnology Information (NCBI) developed "NCBI Orthologs", a resource and a computational pipeline designed to meet this challenge within the NCBI RefSeq framework. This system integrates protein similarity, nucleotide alignment, and microsynteny to achieve high-precision ortholog assignments across diverse eukaryotes. The pipeline leverages high-quality RefSeq annotations and processes genomes individually, ensuring scalability. Resulting ortholog data, organized into gene-level anchored sets, enables propagation of functional annotation information and facilitates comparative genomics. Critically, these data are integrated into the NCBI Gene resource, providing users with access from various entry points. The NCBI Datasets resource provides an intuitive interface to explore orthologous relationships on the web and allows bulk data download via the web, command-line tools, and an API. We detail the methodology, including anchor species selection and the decision tree used to arrive at high-confidence one-to-one orthology relationships. NCBI Orthologs is a valuable resource for facilitating functional annotation efforts and enhancing our understanding of eukaryotic gene evolution.