Biology subjects

Kates, H.

Publications and source records attributed to Kates, H..

3 recordsLinked to original sources

bioRxiv2026

Spatially Resolved Banff Tubulitis and Glomerulitis Scoring in Kidney Allograft Biopsies via Artificial Intelligent-Based Structure Segmentation and Spatial Transcriptomics

BackgroundTubulitis is a defining histologic feature of T cell-mediated rejection (TCMR), while glomerulitis is often characteristic of antibody mediated rejection (AMR). Histologic quantification of tubulitis and glomerulitis using Banff criteria is subject to interobserver variability. Bulk transcriptomic assays (e.g., MMDx) have introduced molecular correlations of tubulitis with TCMR and glomerulitis with AMR, but lack spatial resolution. MethodsWe applied a web-based platform, FUSION (Functional Unit State Identification in Whole Slide Images), to a cohort of 8 cases (n=2 per condition) with kidney allograft biopsy samples acute TCMR, active AMR, chronic active AMR, and no rejection (control). The machine-learning (ML) platform enabled integrated visualization and analysis of spatial transcriptomics (10x Genomics Visium v2) together with high-resolution whole-slide histology. ResultsTranscriptomics-derived immune cell proportions within AI-segmented tubular and glomerular regions were used to generate spatial Banff t- and g-scores. Derived t-scores showed full concordance with pathologist scores in both acute TCMR cases; g-scores showed concordance in 2 of 4 AMR cases, with discordant cases characterized by low absolute immune signal near the classification boundary. ConclusionsWe demonstrate the feasibility of using AI-based FTU segmentation integrated with spatial transcriptomics-derived immune cell proportions to generate spatially informed t- and g-scores aligned with Banff criteria, with full concordance in severe rejection and partial concordance in mild rejection. This approach lays the foundation for validated, spatial transcriptomics-augmented t-scores and g-scores that enhance diagnostic precision, reduces inter-observer variability among renal pathologists, and support potential clinical adoption.

pathology↗

bioRxiv2023

Spatial phylogenetics of Fagales: Investigating the history of temperate forests

AimQuantifying the phylogenetic diversity of temperate trees is essential for understanding what processes are implicated in shaping the modern distribution of temperate broadleaf forest and other major forest biomes. Here we focus on Fagales, an iconic member of forests worldwide, to uncover global diversity and endemism patterns and investigate potential drivers responsible for the spatial distribution of fagalean forest communities. LocationGlobal. TaxonFagales. MethodsWe combined phylogenetic data covering 60.2% of living species, fine-scale distribution models covering 90% of species, and nodulation data covering all species to investigate the distribution of species richness at fine spatial scales and compare this to relative phylogenetic diversity (RPD) and phylogenetic endemism. Further, we quantify phylogenetic betadiversity and bioregionalization of Fagales and determine hotspots of Fagales species engaging in root nodule symbiosis (RNS) with nitrogen-fixing actinomycetes. ResultsWe find the highest richness in temperate east Asia, eastern North America, and equatorial montane regions of Asia and Central America. By contrast, RPD is highest at higher latitudes, where RNS also predominates. We found a strong spatial structuring of regionalizations of Fagales floras as defined by phylogeny and traits related to RNS, reflecting distinct Northern and Southern Hemisphere floras (with the exception of a unique Afro-Boreal region) and highly distinct tropical montane communities. Main conclusionsSpecies richness and phylogenetic regionalization accord well with traditional biogeographic concepts for temperate forests, but RPD does not. This may reflect ecological filtering specific to Fagales, as RNS strategies are almost universal in the highest RPD regions. Our results highlight the importance of global-scale, clade-specific spatial phylogenetics and its utility for understanding the history behind temperate forest diversity.

evolutionary biology↗

bioRxiv2022

Two shifts in evolutionary lability underlie independent gains and losses of root-nodule symbiosis in a single clade of plants

Root nodule symbiosis (RNS) allows plants to access atmospheric nitrogen converted into usable forms through a mutualistic relationship with soil bacteria. RNS is a complex trait requiring coordination from both the plant host and the bacterial symbiont, and pinpointing the evolutionary origins of root nodules is critical for understanding the genetic basis of RNS. This endeavor is complicated by data limitations and the intermittent presence of RNS in a single clade of ca. 30,000 species of flowering plants, i.e., the nitrogen-fixing clade (NFC). We developed the most extensive de novo phylogeny for all major lineages of the NFC and an enhanced root nodule trait database to reconstruct the evolution of RNS. Through identification of the evolutionary pathway to RNS gain, we show that shifts among heterogeneous evolutionary rates can explain how a complex trait such as RNS can arise many times across a large phylogeny. Our analysis identifies a two-step process in which an ancestral precursor state gave rise to a more labile state from which RNS was quickly gained at specific points in the NFC. Our rigorous reconstruction of ancestral states illustrates how a two-step pathway could have led to multiple independent gains and losses of RNS, contrary to recent hypotheses invoking just a single gain and numerous losses. RNS may be an example of multi-level convergent evolution, thus requiring a broader phylogenetic and genetic scope for genome-phenome mapping to elucidate mechanisms enabling fully functional RNS.

evolutionary biology↗