---
title: "SALRR: Scalable Long-Read RNA-Seq Platform for Isoform-Resolved Human Brain Transcriptomics"
id: "biorxiv-17-salrr-scalable-analysis-of-long-read-rna-seq-enables-comprehensive"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-17-salrr-scalable-analysis-of-long-read-rna-seq-enables-comprehensive"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.08.27.747499v1?rss=1"
published_at: "2026-08-29T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# SALRR: Scalable Long-Read RNA-Seq Platform for Isoform-Resolved Human Brain Transcriptomics
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-17-salrr-scalable-analysis-of-long-read-rna-seq-enables-comprehensive
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.08.27.747499v1?rss=1)
- **Published At:** 2026-08-29T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study introduces **SALRR** (Scalable Analysis of Long-Read RNA-seq), an integrated wet-lab and computational platform designed for population-scale, isoform-resolved transcriptomics in human brain tissue. - Automated cDNA library preparation using Oxford Nanopore Technologies (ONT) chemistry on the Hamilton Microlab NGS STAR reduces hands-on time by 67% and supports preparation of 24 libraries per operator per day while preserving performance across RNA integrity values. - The computational workflow is a modular, Snakemake-based pipeline that performs end-to-end processing from ONT signal data to isoform-level quantification, includes SIRV spike-in calibration, multi-stage quality control, and stringent isoform validation. - Applied to 10 postmortem frontal cortex samples from the North American Brain Expression Consortium, SALRR identified 31,607 high-confidence isoforms across 10,075 genes. - Among identified isoforms, 8,532 were novel splice variants not present in **GENCODE v49**, indicating substantial previously unannotated transcript diversity in human brain. - SALRR detected complex splicing events at loci relevant to neurodegeneration—examples include **GBA1**, **CCNF**, **CHCHD10**, and **TREM2**—events that were systematically missed by short-read sequencing. - All protocols and code for both the automated wet-lab workflow and the computational pipeline are openly available, aiming to provide a scalable, community-ready framework for studies of neurodegeneration, aging, and complex brain disease. - The platform addresses prior barriers to population-scale long-read RNA-seq: labor-intensive library prep, sensitivity to RNA degradation in postmortem tissue, and lack of integrated reproducible analysis pipelines. - The authors declare no competing interests and list NIH and ZIA funding identifiers; the preprint is available via bioRxiv under a CC0 license.
## Clinical Analysis & Structured Key Points
SALRR: Scalable Analysis of Long-Read RNA-Seq Enables Comprehensive Transcriptome Profiling in Human Brain | bioRxiv Skip to main content New Results SALRR: Scalable Analysis of Long-Read RNA-Seq Enables Comprehensive Transcriptome Profiling in Human Brain Cedric Kouam , Jackson Mingle , Pilar Alvarez Jerez , Allison Evans , Abraham Moller , Breeana Baker , Cory Weller , Kimberly Paquette , Janet Brooks , Spencer M Grant , Alexis Ayuketah , Melissa Meredith , Joanna Palade , Laksh Malik , Kristen Hise , View ORCID Profile J. Raphael Gibbs , Jessica Anderson , Jinhui Ding , Robert Harbert , Yilei Fu , View ORCID Profile Xinchang Zheng , Sonia Garcia-Ruiz , Emil K Gustavsson , Cornelis Blauwendraat , Mina Ryten , Fritz Sedlazeck , Luigi Ferrucci , Xylena Reed , Mike A. Nalls , View ORCID Profile Mark R Cookson , Kendall Van Keuren-Jensen , Elizabeth Hutchins , View ORCID Profile Miten Jain , View ORCID Profile Kimberley J Billingsley doi: https://doi.org/10.64898/2026.08.27.747499 Cedric Kouam 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jackson Mingle 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Pilar Alvarez Jerez 2 GP2; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Allison Evans 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abraham Moller 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Breeana Baker 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Cory Weller 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kimberly Paquette 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Janet Brooks 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Spencer M Grant 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alexis Ayuketah 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Melissa Meredith 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Joanna Palade 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Laksh Malik 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kristen Hise 3 Hamilton Company; Find this author on Google Scholar Find this author on PubMed Search for this author on this site J. Raphael Gibbs 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for J. Raphael Gibbs Jessica Anderson 4 Oxford Nanopore Technologies; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jinhui Ding 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Robert Harbert 4 Oxford Nanopore Technologies; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yilei Fu 5 Baylor College of Medicine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Xinchang Zheng 5 Baylor College of Medicine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Xinchang Zheng Sonia Garcia-Ruiz 6 University of Cambridge; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Emil K Gustavsson 6 University of Cambridge; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Cornelis Blauwendraat 7 CAS; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mina Ryten 6 University of Cambridge; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Fritz Sedlazeck 5 Baylor College of Medicine; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Luigi Ferrucci 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Xylena Reed 8 National Institute on Aging; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mike A. Nalls 9 National Institutes of Health; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mark R Cookson 8 National Institute on Aging; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Mark R Cookson Kendall Van Keuren-Jensen 10 Tgen: Translational Genomics Research Institute; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Elizabeth Hutchins 11 Translational Genomics Research Institute; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Miten Jain 12 Northeastern University Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Miten Jain For correspondence: mi.jain{at}northeastern.edu Kimberley J Billingsley 1 NIH; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kimberley J Billingsley Abstract Info/History Metrics Supplementary material Preview PDF Abstract Isoform-resolved transcriptomics is fundamental to decoding the molecular complexity of the human brain, yet population-scale long-read RNA sequencing has remained inaccessible due to labor-intensive library preparation, sensitivity to RNA degradation in postmortem tissue, and the absence of integrated, reproducible analysis pipelines. Here we present SALRR (Scalable Analysis of Long-Read RNA-seq), an integrated wet-lab and computational platform designed to overcome these barriers. Automated ONT long-read cDNA library preparation on the Hamilton Microlab NGS STAR platform reduces hands-on time by 67% and enables 24 libraries per operator per day while maintaining performance across RNA integrity values. A modular, Snakemake-based pipeline performs end-to-end processing from ONT signal data to isoform-level quantification, incorporating SIRV spike-in calibration, multi-stage quality control, and stringent isoform validation. Applied to 10 postmortem frontal cortex samples from the North American Brain Expression Consortium, SALRR identified 31,607 high-confidence isoforms from 10,075 genes, including 8,532 novel splice variants absent from GENCODE v49, and complex splicing events systematically missed by short-read sequencing at neurodegeneration-relevant loci, including GBA1, CCNF, CHCHD10, and TREM2. All protocols and code are openly available, providing a scalable, community-ready framework for isoform-resolved transcriptomics in neurodegeneration, aging, and complex brain disease. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared NIH , ZIAAG000534 , ZIAAG000538 , ZIAHG200398 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. Back to top Previous Next Posted August 29, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following SALRR: Scalable Analysis of Long-Read RNA-Seq Enables Comprehensive Transcriptome Profiling in Human Brain Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share SALRR: Scalable Analysis of Long-Read RNA-Seq Enables Comprehensive Transcriptome Profiling in Human Brain Cedric Kouam , Jackson Mingle , Pilar Alvarez Jerez , Allison Evans , Abraham Moller , Breeana Baker , Cory Weller , Kimberly Paquette , Janet Brooks , Spencer M Grant , Alexis Ayuketah , Melissa Meredith , Joanna Palade , Laksh Malik , Kristen Hise , J. Raphael Gibbs , Jessica Anderson , Jinhui Ding , Robert Harbert , Yilei Fu , Xinchang Zheng , Sonia Garcia-Ruiz , Emil K Gustavsson , Cornelis Blauwendraat , Mina Ryten , Fritz Sedlazeck , Luigi Ferrucci , Xylena Reed , Mike A. Nalls , Mark R Cookson , Kendall Van Keuren-Jensen , Elizabeth Hutchins , Miten Jain , Kimberley J Billingsley bioRxiv 2026.08.27.747499; doi: https://doi.org/10.64898/2026.08.27.747499 Share This Article: Copy Citation Tools SALRR: Scalable Analysis of Long-Read RNA-Seq Enables Comprehensive Transcriptome Profiling in Human Brain Cedric Kouam , Jackson Mingle , Pilar Alvarez Jerez , Allison Evans , Abraham Moller , Breeana Baker , Cory Weller , Kimberly Paquette , Janet Brooks , Spencer M Grant , Alexis Ayuketah , Melissa Meredith , Joanna Palade , Laksh Malik , Kristen Hise , J. Raphael Gibbs , Jessica Anderson , Jinhui Ding , Robert Harbert , Yilei Fu , Xinchang Zheng , Sonia Garcia-Ruiz , Emil K Gustavsson , Cornelis Blauwendraat , Mina Ryten , Fritz Sedlazeck , Luigi Ferrucci , Xylena Reed , Mike A. Nalls , Mark R Cookson , Kendall Van Keuren-Jensen , Elizabeth Hutchins , Miten Jain , Kimberley J Billingsley bioRxiv 2026.08.27.747499; doi: https://doi.org/10.64898/2026.08.27.747499 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Genomics Subject Areas All Articles Animal Behavior and Cognition (7945) Biochemistry (18565) Bioengineering (14718) Bioinformatics (43981) Biophysics (22375) Cancer Biology (19499) Cell Biology (26670) Clinical Trials (138) Developmental Biology (13855) Ecology (20805) Epidemiology (2067) Evolutionary Biology (25250) Genetics (16067) Genomics (23351) Immunology (18528) Microbiology (42092) Molecular Biology (17885) Neuroscience (92579) Paleontology (691) Pathology (2958) Pharmacology and Toxicology (5051) Physiology (8029) Plant Biology (15846) Scientific Communication and Education (2090) Synthetic Biology (4523) Systems Biology (10156) Zoology (2368)
## Related Clinical Research

- [Characteristics, Comorbidities, Medications, and Resource Use in Patients Newly Diagnosed with Alz](https://medichelpline.com/clinical-feed/bmj-open-5-characterising-patients-with-alzheimers-disease-in-england-a-cohort-study-using.md)
- [Pharmacist-led SPOS reduces polypharmacy and drug costs in acute ischemic stroke without harming r](https://medichelpline.com/clinical-feed/plos-one-5-impact-of-a-pharmacist-led-optimization-strategy-for-cerebrovascular.md)
- [Federal autism advisory committee highlights vaccines and shifts research priorities away from gen](https://medichelpline.com/clinical-feed/stat-news-2-at-a-federal-autism-advisory-committee-meeting-members-double-down-on-long.md)
- [MTHFR 677C>T variant drives prodromal cerebrovascular and synaptic signatures in a mouse model of](https://medichelpline.com/clinical-feed/biorxiv-0-mthfr-677c-t-produces-distinct-prodromal-disease-signatures-in-a-mouse-model-of.md)
- [Contextual inference controls protection or disruption of motor memory](https://medichelpline.com/clinical-feed/biorxiv-14-contextual-inference-drives-motor-memory-protection-and-disruption.md)

## Navigation
- [← Back to Neurology Feed](https://medichelpline.com/clinical-feed/neurology.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.