Biology subjects

Yates, B.

Publications and source records attributed to Yates, B..

4 recordsLinked to original sources

bioRxiv2025

AI for IACUC: Accurate Initial Assessment of Institutional Animal Care and Use Committee Protocols

Every animal protocol requires careful review to ensure humane principles, laws, and policies are followed before any experiments may be performed. Developing protocols and receiving approval can be a lengthy process requiring multiple rounds of feedback and refinement. Artificial Intelligence (AI) has the potential to improve the quality and speed of IACUC protocol reviews by detecting submission errors. We describe an approach to achieve this and show that our approach can be replicated, while addressing issues of ethics and bias, robustness, and trustworthiness1. Replication is addressed by developing a template and demonstrating that it can be reused. Ethics and bias issues are addressed by early, limited use of a large language Model (LLM) to identify errors and rapidly provide useful feedback to the protocol developer. In our approach, subsequent steps still require a review by the IACUC board, which retains ethical responsibility for approval. Robustness and trustworthiness were evaluated by using the template that is replicated for eleven distinct checks and performed on 50 new protocols using two different LLMs. We show that every actual problem in those submissions (within the test parameters) is found by our AI review (i.e., recall=100%), giving IACUC boards confidence in the utility of our system. In addition, precision for our checks is between 80%-100%, with most being 100%, thereby making the system a practical compliment to administrative protocol review for those submitting. Overall, we report F1 scores of between 89-100%.

scientific communication and education↗

bioRxiv2024

IKAROS facilitates antigen escape in the face of CD19- and CD22-targeted therapies for B-cell acute lymphoblastic leukemia

Relapse due to antigen escape is a major cause of treatment failure for patients with B-cell malignancies following targeted immunotherapies, including CD19- and CD22-directed chimeric antigen receptor T (CAR T) cells. To identify tumor intrinsic factors associated with antigen loss, we performed single-cell analyses on 61 primary patient samples or patient-derived xenografts from patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with CAR T cells. We identified that low levels of the transcription factor IKAROS in pro-B-like B-ALL cells before CAR T treatment are associated with antigen escape. We demonstrate that IKAROSlow B-ALL cells lose features of B cell identity and resemble progenitor cells based on their epigenetic and transcriptional state, resulting in the downregulation of B-cell immunotherapy antigens, including surface expression of CD19 and CD22. We find that modulation of CD19 and CD22 protein expression is IKAROS dose-dependent and reversible. Further, we demonstrate that IKAROSlow cells are resistant to CD19- and CD22-targeted therapies. Together, we describe a novel role for IKAROS in the regulation of B-cell immunotherapy targets and the risk of antigen escape relapse, identifying it as a potential prognostic target. HighlightsO_LIIKAROSlow pro-B-like B-ALL cells are associated with CD19neg relapse C_LIO_LIIKAROSlow B-ALL cells resemble progenitor cells and have lower B-cell commitment C_LIO_LIIKAROS modulates CD19 and CD22 surface expression in a dose-dependent and reversible manner C_LIO_LIIKAROSlow B-ALL cells are more resistant to CD19- and CD22-targeted therapies C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/621347v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@109f75eorg.highwire.dtl.DTLVardef@14f41fborg.highwire.dtl.DTLVardef@74e428org.highwire.dtl.DTLVardef@2f275c_HPS_FORMAT_FIGEXP M_FIG C_FIG Before immunotherapy, IKAROSlow pro-B-like B-ALL cells possess chromatin and gene expression states poised for loss of B-cell identity while maintaining expression of CD19 and CD22. Under immune pressure, IKAROShigh cells maintain their antigen expression, making them more susceptible to T cell-mediated killing. Conversely, IKAROSlow cells are more likely to downregulate their antigen expression, giving them a relative advantage to escape immunotherapies, resulting in antigen escape relapse.

cancer biology↗

bioRxiv2022

The VGNC: Expanding Standardized Vertebrate Gene Nomenclature

The Vertebrate Gene Nomenclature Committee (VGNC) was established in 2016 as a sister project to the HGNC (HUGO Gene Nomenclature Committee), to approve gene nomenclature in vertebrate species without an existing dedicated nomenclature committee. The VGNC aims to harmonize gene nomenclature across selected vertebrate species in line with human gene nomenclature, with orthologs assigned the same nomenclature where possible. This article presents an overview of the VGNC project and discussion of key findings resulting from this work to date. VGNC approved nomenclature is accessible at https://vertebrate.genenames.org, and is additionally displayed by the NCBI, Ensembl and UniProt databases.

genomics↗

bioRxiv2020

Natural variation in autumn FLC levels, rather than epigenetic silencing, aligns vernalization to different climates

Plants monitor temperatures over long timescales to assess seasons and time developmental transitions. In Arabidopsis thaliana, winter is registered during vernalization through the temperature-dependent repression and epigenetic silencing of floral repressor FLOWERING LOCUS C (FLC). Natural Arabidopsis accessions show considerable variation in vernalization, however which aspect of the FLC repression mechanism is most important for adaptation to different climates is not clear. By analyzing FLC silencing in natural variants throughout winter in three field sites, we find that FLC starting levels and early phases of silencing are the major variables underlying vernalization response, rather than establishment of epigenetic silencing. This results in an intricate interplay between promotion and delay of flowering to balance survival, and through a post-vernalization effect of FLC, reproductive effort via branch production. These data reveal how non-coding FLC variation aligns vernalization response to different climatic conditions and year-on-year fluctuations in natural temperature profiles. Impact StatementAlleles of the major floral repressor vary in their initial expression to underpin the ability of Arabidopsis to survive year-on-year climatic fluctuations.

molecular biology↗