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Gratton, B.

Publications and source records attributed to Gratton, B..

2 recordsLinked to original sources

Anatolution, an online platform for consensus morphology

IntroductionSupervised statistical learning for cell-level segmentation and morphometry in optical microscopy is limited less by algorithmic capacity than by the scarcity of reliable, expert-validated ground truth. In comparative neuroscience and quantitative histology, where classical stains such as Nissls method remain the primary means to study cellular morphology, this bottleneck is acute: manual annotation is expensive, subject to individual bias, and rarely performed at the scale or consistency that computational approaches demand. No existing platform integrates a stain-specific bioimage segmentation protocol, a structured multi-annotator workflow, and consensus-based quality control into a single pipeline from image ingestion to machine-readable training data. MethodsWe present Anatolution, an open-source, web-based platform designed to address the gap of quality annotations at https://anatolution.herokuapp.com/public-tool/. Anatolution organizes microscopy images, including 2D arrays or 3D volumes, into project workspaces where multiple annotators independently label cellular structures against a shared computer vision catalogue. This design enables systematic inter-rater and intra-rater reliability assessment, with consensus derived from agreement across annotators rather than from any single experts judgment. The platform enables the export of aggregated labels or annotation datasets for downstream statistical learning methods. We describe the systems architecture, its Nissl-specific segmentation pipeline, the consensus annotation workflow, and validation of inter-rater reliability. ConclusionAcross 20+ histological annotation containers annotated by up to 15 independent raters, consensus boundary agreement increased monotonically with annotator count, reaching a median Dice of 0.79 against the full-rater reference at seven annotators, with top-tier containers achieving leave-one-out ceiling values of 0.621-0.769 for cell-body segmentation. The segmentation pipeline provided effective spatial anchoring, with 88% of consensus-annotated polygons containing at least one algorithmically detected seed. Anatolution provides open-source infrastructure for producing consensus-validated training data from classical histological preparations, addressing the primary bottleneck limiting supervised learning for cell-level morphometry.

neuroscience↗

FLT3 is genetically essential for ITD-mutated leukemic stem cells but dispensable for human hematopoietic stem cells

Leukemic stem cells (LSCs) fuel acute myeloid leukemia (AML) growth and relapse, but therapies tailored towards eradicating LSCs without harming healthy hematopoietic stem cells (HSCs) are lacking. FLT3 is considered an important therapeutic target due to frequent mutation in AML and association with relapse. However, there has been limited clinical success with FLT3 targeting, suggesting either that FLT3 is not a vulnerability in LSC, or that more potent inhibition is required, a scenario where HSC toxicity could become limiting. We tested these possibilities by ablating FLT3 using CRISPR/Cas9-mediated FLT3 knock-out (FLT3-KO) in human LSCs and HSCs followed by functional xenograft assays. FLT3-KO in LSCs from FLT3-ITD mutated, but not FLT3-WT AMLs, resulted in short-term leukemic grafts of FLT-3-KO edited cells that disappeared by 12 weeks. By contrast, FLT3-KO in HSCs from fetal liver, cord blood and adult bone marrow did not impair multilineage hematopoiesis in primary and secondary xenografts. Our study establishes FLT3 as an ideal therapeutic target where ITD+ LSC are eradicated upon FLT3 deletion, while HSCs are spared. These findings support the development of more potent FLT3-targeting drugs or gene-editing approaches for LSC eradication to improve clinical outcomes. KEY POINTSThe FLT3 gene is essential for ITD-mutated leukemic stem cells (LSCs) to establish and propagate leukemia. Normal human hematopoietic stem cells (HSCs) do not require FLT3 to engraft and sustain hematopoiesis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=179 SRC="FIGDIR/small/601363v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@b77f56org.highwire.dtl.DTLVardef@109011dorg.highwire.dtl.DTLVardef@282e04org.highwire.dtl.DTLVardef@1e51e3b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗