Evidence map›Paper›PMID 40593860›Full record

ArticleNPJ genomic medicine2025

Assessing the diagnostic impact of blood transcriptome profiling in a pediatric cohort previously assessed by genome sequencing.

Huayun Hou, Kyoko E Yuki, Gregory Costain, Anna Szuto, Sierra Barnes, Arun K Ramani, Alper Celik, Michael Braga, Meagan Gloven-Brown, Dimitri J Stavropoulos and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ genomic medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Huayun Hou *Program in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
Kyoko E Yuki *Program in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
Gregory CostainProgram in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
Anna SzutoProgram in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
Sierra BarnesDivision of Genome Diagnostics, The Hospital for Sick Children, Toronto, ON, Canada.
Arun K RamaniCentre for Computational Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Alper CelikCentre for Computational Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Michael BragaDivision of Genome Diagnostics, The Hospital for Sick Children, Toronto, ON, Canada.
Meagan Gloven-BrownDivision of Genome Diagnostics, The Hospital for Sick Children, Toronto, ON, Canada.
Dimitri J StavropoulosDivision of Genome Diagnostics, The Hospital for Sick Children, Toronto, ON, Canada.
Sarah BowdinDivision of Genome Diagnostics, The Hospital for Sick Children, Toronto, ON, Canada.
Ronald D CohnProgram in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
Roberto Mendoza-LondonoDivision of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, Canada.
Stephen W SchererProgram in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
Michael BrudnoProgram in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
Christian R MarshallDivision of Genome Diagnostics, The Hospital for Sick Children, Toronto, ON, Canada.
M Stephen MeynCenter for Human Genomics and Precision Medicine, University of Wisconsin, Madison, WI, USA.
Adam ShlienProgram in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
James J DowlingProgram in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada.
Michael D WilsonProgram in Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada. michael.wilson@sickkids.ca.
Lianna KyriakopoulouDivision of Genome Diagnostics, The Hospital for Sick Children, Toronto, ON, Canada. lianna.kyriakopoulou@sickkids.ca.

Funding

Genome Canada OGI-158
6 · The paper itself

Abstract

Despite advances in genome sequencing, many individuals with rare genetic disorders remain undiagnosed. Transcriptional profiling via RNA-seq can reveal functional impacts of DNA variants and improve diagnosis. We assessed blood-derived RNA-seq in the largely undiagnosed SickKids Genome Clinic cohort (n = 134), which has been subjected to multiple analyses benchmarking the utility of genome sequencing. Our RNA-centric analysis identifies gene expression outliers, aberrant splicing, and allele-specific expression. In one-third of diagnosed individuals (20/61), RNA-seq reinforced DNA-based findings. In 2/61 cases, RNA-seq revised diagnoses (EPG5 to LZTR1 in an individual with a Noonan syndrome-like disorder) and discovered an additional relevant gene (CEP120 in addition to SON in an individual with ZTTK syndrome). Additionally, ~7% (5/73) of undiagnosed cases had at least one plausible candidate gene identified. This study highlights both the benefits and limitations of whole-blood RNA profiling in refining genetic diagnoses and uncovering novel disease mechanisms.

Identifiers

PMID40593860
PMCPMC12215727

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.