Evidence map›Paper›PMID 34404843›Full record

ArticleScientific reports2021

Single cell morphology distinguishes genotype and drug effect in Hereditary Spastic Paraplegia.

Gautam Wali, Shlomo Berkovsky, Daniel R Whiten, Alan Mackay-Sim, Carolyn M Sue

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.2field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 26 citations in OpenAlex.

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  10. Reduced acetylated α-tubulin inFrontiers in neuroscience · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Gautam WaliDepartment of Neurogenetics, Kolling Institute of Medical Research, The University of Sydney, Sydney, NSW, 2065, Australia. gautam.wali@sydney.edu.au.
Shlomo BerkovskyCentre for Health Informatics, Macquarie University, Sydney, Australia.
Daniel R WhitenDepartment of Neurogenetics, Kolling Institute of Medical Research, The University of Sydney, Sydney, NSW, 2065, Australia.
Alan Mackay-Sim *Department of Neurogenetics, Kolling Institute of Medical Research, The University of Sydney, Sydney, NSW, 2065, Australia.
Carolyn M Sue *Department of Neurogenetics, Kolling Institute of Medical Research, The University of Sydney, Sydney, NSW, 2065, Australia.
University of Sydney · AUMacquarie University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A central need for neurodegenerative diseases is to find curative drugs for the many clinical subtypes, the causative gene for most cases being unknown. This requires the classification of disease cases at the genetic and cellular level, an understanding of disease aetiology in the subtypes and the development of phenotypic assays for high throughput screening of large compound libraries. Herein we describe a method that facilitates these requirements based on cell morphology that is being increasingly used as a readout defining cell state. In patient-derived fibroblasts we quantified 124 morphological features in 100,000 cells from 15 people with two genotypes (SPAST and SPG7) of Hereditary Spastic Paraplegia (HSP) and matched controls. Using machine learning analysis, we distinguished between each genotype and separated them from controls. Cell morphologies changed with treatment with noscapine, a tubulin-binding drug, in a genotype-dependent manner, revealing a novel effect on one of the genotypes (SPG7). These findings demonstrate a method for morphological profiling in fibroblasts, an accessible non-neural cell, to classify and distinguish between clinical subtypes of neurodegenerative diseases, for drug discovery, and potentially for biomarkers of disease severity and progression.

Indexed as

GenotypePharmaceutical PreparationsATPases Associated with Diverse Cellular ActivitiesDisease ProgressionHumansMachine LearningMetalloendopeptidasesMutationSeverity of Illness IndexSingle-Cell AnalysisSpastic Paraplegia, HereditarySpastinATPases Associated with Diverse Cellular ActivitiesMetalloendopeptidasesPharmaceutical PreparationsSpastinSPAST protein, humanSPG7 protein, human

Identifiers

PMID34404843
PMCPMC8371156
OpenAlexW3195939922

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.