Applying single‐cell technologies to clinical pathology: progress in nephropathology
Bibliographic record
Abstract
Cells represent the basic building blocks of living organisms. Accurate characterisation of cellular phenotype, intercellular signalling networks, and the spatial organisation of cells within organs is crucial to deliver a better understanding of the processes underpinning physiology, and the perturbations that lead to disease. Single-cell methodologies have increased rapidly in scale and scope in recent years and are set to generate important insights into human disease. Here, we review current practices in nephropathology, which are dominated by relatively simple morphological descriptions of tissue biopsies based on their appearance using light microscopy. Bulk transcriptomics have more recently been used to explore glomerular and tubulointerstitial kidney disease, renal cancer, and the responses to injury and alloimmunity in kidney transplantation, generating novel disease insights and prognostic biomarkers. These studies set the stage for single-cell transcriptomic approaches that reveal cell-type-specific gene expression patterns in health and disease. These technologies allow genome-wide disease susceptibility genes to be interpreted with the knowledge of the specific cell populations within organs that express them, identifying candidate cell types for further study. Single-cell technologies are also moving beyond assaying individual cellular transcriptomes, to measuring the epigenetic landscape of single cells. Single-cell antigen-receptor gene sequencing also enables specific T- and B-cell clones to be tracked in different tissues and disease states. In the coming years these rich 'multi-omic' descriptions of kidney disease will enable histopathological descriptions to be comprehensively integrated with molecular phenotypes, enabling better disease classification and prognostication and the application of personalised treatment strategies. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.004 | 0.002 |
| Science and technology studies | 0.001 | 0.004 |
| Scholarly communication | 0.005 | 0.005 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.003 | 0.005 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".