Svetlana Gorokhova

Clinical long-read genome sequencing for rare disease diagnostics Background Diagnostic evaluation of rare genetic disorders continues to rely on multiple test modalities, despite the increasing use of short-read exome or genome sequencing as first-tier tests. Long-...

1,000 PacBio genomes in a prospectively designed clinical utility study.
This was the biggest and most important study that made us go live in diagnostics.

Long-read genomes as a genetic first tier test across many rare diseases!
www.medrxiv.org/content/10.6...

Evaluating the effects of archaic protein-altering variants in living human adults Promise and pitfalls of using large biobanks to study impacts of archaic protein-coding variants in living humans.

While stories of singular DNA changes that drove evolution of human brain/behaviour remain seductive, advances across multiple fields of biology cast doubt on such simplistic narratives of our origins. A new paper from my lab shows how biobanks may speak to this fundamental question.🧪
Explainer🧵👇1/n

BRAIN-MAGNET: A functional genomics atlas for interpretation of non-coding variants BRAIN-MAGNET, a convolutional neural network trained on 148,198 functionally tested non-coding regulatory elements, predicts enhancer activity directly from DNA sequence and identifies nucleotides ess...

Very pleased to share our latest paper published in Cell:
BRAIN-MAGNET: A functional genomics atlas for interpretation of non-coding variants: Cell www.cell.com/cell/fulltex...
@cellpress.bsky.social, @cp-cell.bsky.social, @ruizhideng.bsky.social #enhancer
here is a thread about our findings:

PolyA_DB v4: systematic polyA site identification and isoform annotation in human and mouse genomes using 3′ end and long-read sequencing data.#PolyA #IsoformAnnotation #Genomics #Bioinformatics #NAR @narjournal.bsky.social 🧪🧬 🖥️
academic.oup.com/nar/advance-...

RBMX functional retrocopy safeguards brain development Retrotransposition has generated thousands of intronless gene copies in mammalian genomes, yet their contribution to brain development and evolution remains largely unexplored. Here we uncover a criti...

I am delighted to finally share our new preprint exploring the role of RBMX and its retrocopies in neurodevelopment:

👉🏻Read the full preprint here:

www.medrxiv.org/content/10.1...

Below are the key findings 👇🏻

Great start of the World Muscle Society #WMS2025 meeting in Vienna - an impressive wheelchair soccer match during the opening ceremony and Society’s 30y anniversary cake this morning! Now to the science with the first session on multisystemic alterations in muscle disease www.wms2025.com

Cellular quality control in humans decoded A research team at the University of Cologne and the Max Delbrück Center in Berlin has deciphered in detail the rules behind an important mechanism of cellular quality control in humans / Publication ...

🧐 This is how quality control works in our cells 🧬

Researchers from the #unicologne and the @mdc-berlin.bsky.social have cracked the code of a crucial mechanism of cellular quality control in humans. 👇
uni.koeln/RRCLZ

Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies Variants in spliceosomal small nuclear RNA (snRNA) genes RNU4-2 (ReNU syndrome), RNU5B-1 , and RNU2-2 have recently been linked to dominant neurodevelopmental disorders (NDDs), revealing a major, prev...

After our study on RNU4-2 and RNU5B-1 published in May (Nava et al, Nature Genetics 2025), I am excited to share our new preprint reporting dominant and recessive variants in RNU2-2 as a frequent cause of developmental and epileptic encephalopathy (DEE).

📄 www.medrxiv.org/content/10.1...

There is a new term that describes a translated region - "translon". This replaces multiple terms, such as ORF, CDS, non-canonical ORF etc.

There's a new nomenclature for a translated region - "translon". This replaces multiple other terms, such as ORF, CDS, non-canonical ORF etc.

DMD duplications on carrier screening are not always pathogenic. Many are interspersed and benign. Assuming tandem equals disease risks misclassification. Long read sequencing reveals structure and can prevent unnecessary interventions. bit.ly/3HI4b2v

This is a great reminder of the pitfalls of precomputed SpliceAI scores.. and a solution to quickly identify the variants that need to be re-annotated with SpliceAI github.com/Computationa...

Also, check out the News & Views summarizing our findings, written by Youjia Guo & @themodzlab.bsky.social 🤩🤩
www.nature.com/articles/s41...

Excited to launch our AlphaGenome API goo.gle/3ZPUeFX along with the preprint goo.gle/45AkUyc describing and evaluating our latest DNA sequence model powering the API. Looking forward to seeing how scientists use it! @googledeepmind

Mapping MAVE data for use in human genomics applications - Genome Biology Background Experimental data from functional assays have a critical role in interpreting the impact of genetic variants. Assay data must be unambiguously mapped to a reference genome to make it access...

We are pleased to announce the publication of our manuscript "Mapping MAVE data for use in human genomics applications" in Genome Biology! 🧵 1/3 genomebiology.biomedcentral.com/articles/10....

Realizing the promise of genome-wide association studies for effector gene prediction - Nature Genetics This Perspective argues that predicting effector genes for complex diseases is a key outcome of genetic association studies where standards are urgently needed to maximize utility, improve interoperab...

🚨Interested in which genes are the true effectors behind the scenes of the #gwas results? 🚨
This new publication in Nature Genetics, a collaboration between @broadinstitute.org @ebi.embl.org @opentargets.org focuses on approaches to predicted effector gene reporting tinyurl.com/98yxy4hf (1/3) 👇

Thanks to this new exome sequencing study, the number of genes with possible "human knockouts" goes up to 2,991!

Cutting the diagnosis journey for children born with rare genetic diseases Families can wait years for a diagnosis of a rare genetic disorder, but a new test can provide answers in days for a better understanding of the condition and potentially earlier treatment, finds new...

We're super proud to see our study showing utility of proteomics in ultra-rapid variant prioritisation for suspected mito and other rare diseases out in Genome Medicine (rdcu.be/endwE). Too many amazing collabs to thank, so here are the big ones @daniellahock.bsky.social @thorburnmito.bsky.social!

Our recent paper is out: Distinct rates of VUS reclassification are observed when subclassifying VUS by evidence level buff.ly/Z0DcO9Q If you don't have access, our preprint is here buff.ly/z8UvVtY This paper emphasizes the critical benefit of VUS subclassification for physicians and patients.

Systematic identification of disease-causing promoter and untranslated region variants in 8040 undiagnosed individuals with rare disease - Genome Medicine Background Both promoters and untranslated regions (UTRs) have critical regulatory roles, yet variants in these regions are largely excluded from clinical genetic testing due to difficulty in interpre...

I am delighted to share with you the news that our shiny new paper has hit the shelves in Genome Medicine!!

link.springer.com/article/10.1...

Key points (A 🧵):

These new SGE (saturation genome editing) scores will definitely be useful to resolve the RNU4-2 VUSes in our patients!

🚨 Big news at #ACMG2025! 🚨
Today we’re announcing global democratization of deidentified allele count + frequency data with population breakdown from the first ~250k short-read WGS in All of Us designed to plug straight into clinical workflows. It is ~1.1 billion unique variants! 🧬💡
🧵 (1/4)

DECIPHER version 11.30 has been released. See the new features at www.deciphergenomics.org #variantinterpretation

Unpicking non-coding genetic variation: Structure-guided modelling holds promise for evaluating how single nucleotide variants affect transcription factor binding. www.biorxiv.org/content/10.1.... @uoe-igc.bsky.social