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High-throughput muscle fiber typing from RNA sequencing data

Oskolkov, Nikolay (author)
Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Bioinformatik,Forskargrupper vid Lunds universitet,LTH profilområde: Teknik för hälsa,LTH profilområden,Lunds Tekniska Högskola,Department of Clinical Sciences, Malmö,Faculty of Medicine,Bioinformatics,Lund University Research Groups,LTH Profile Area: Engineering Health,LTH Profile areas,Faculty of Engineering, LTH,Lund Univ, Dept Clin Sci, Malmö, Sweden.;Lund Univ, Dept Biol, Sci Life Lab, Natl Bioinformat Infrastruct Sweden, Lund, Sweden.
Santel, Malgorzata (author)
Max Planck Institute for Evolutionary Anthropology,Max Planck Inst Evolutionary Anthropol, Leipzig, Germany.
Parikh, Hemang M. (author)
University of South Florida,Univ S Florida, Hlth Informat Inst, Morsani Coll Med, Gainesville, FL USA.
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Ekström, Ola (author)
Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Lund Univ, Dept Clin Sci, Malmö, Sweden.
Camp, Gray J. (author)
Max Planck Institute for Evolutionary Anthropology,Max Planck Inst Evolutionary Anthropol, Leipzig, Germany.
Miyamoto-Mikami, Eri (author)
Juntendo University,Juntendo Univ, Grad Sch Hlth & Sports Sci, Chiba, Japan.
Ström, Kristoffer (author)
Mittuniversitetet,Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Mid Sweden University, Östersund,Institutionen för hälsovetenskaper (HOV),Lund Univ, Dept Clin Sci, Malmö, Sweden.;Mid Sweden Univ, Swedish Winter Sports Res Ctr, Östersund, Sweden.,Swedish Winter Sports Research Centre
Mir, Bilal Ahmad (author)
Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Lund Univ, Dept Clin Sci, Malmö, Sweden.
Kryvokhyzha, Dmytro (author)
Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,Lund Univ, Dept Clin Sci, Malmö, Sweden.
Lehtovirta, Mikko (author)
Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki,Lund Univ, Dept Clin Sci, Malmö, Sweden.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
Kobayashi, Hiroyuki (author)
University of Tsukuba Hospital,Tsukuba Univ Hosp, Mito Med Ctr, Ibaraki, Japan.
Kakigi, Ryo (author)
Josai International University,Josai Int Univ, Fac Management & Informat Sci, Chiba, Japan.
Naito, Hisashi (author)
Juntendo University,Juntendo Univ, Grad Sch Hlth & Sports Sci, Chiba, Japan.
Eriksson, Karl Fredrik (author)
Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Vaskulära sjukdomar - kliniska studier,Translational Muscle Research,Lund University Research Groups,Vascular Diseases - Clinical Research,Lund Univ, Dept Clin Sci, Malmö, Sweden.
Nystedt, Björn, 1978- (author)
Uppsala universitet,Uppsala University,Uppsala Univ, Dept Cell & Mol Biol, Sci Life Lab, Natl Bioinformat Infrastruct Sweden, Uppsala, Sweden.,Molekylär evolution,Science for Life Laboratory, SciLifeLab
Fuku, Noriyuki (author)
Juntendo University,Juntendo Univ, Grad Sch Hlth & Sports Sci, Chiba, Japan.
Treutlein, Barbara (author)
Max Planck Institute for Evolutionary Anthropology,Max Planck Inst Evolutionary Anthropol, Leipzig, Germany.
Pääbo, Svante (author)
Max Planck Institute for Evolutionary Anthropology,Max Planck Inst Evolutionary Anthropol, Leipzig, Germany.;Okinawa Inst Sci & Technol, Onna Son, Japan.
Hansson, Ola (author)
Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki,Lund Univ, Dept Clin Sci, Malmö, Sweden.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
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 (creator_code:org_t)
2022-07-02
2022
English.
In: Skeletal Muscle. - : Springer Science and Business Media LLC. - 2044-5040. ; 12, s. 1-9
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Background: Skeletal muscle fiber type distribution has implications for human health, muscle function, and performance. This knowledge has been gathered using labor-intensive and costly methodology that limited these studies. Here, we present a method based on muscle tissue RNA sequencing data (totRNAseq) to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for a larger number of individuals to be tested. Methods: By using single-nuclei RNA sequencing (snRNAseq) data as a reference, cluster expression signatures were produced by averaging gene expression of cluster gene markers and then applying these to totRNAseq data and inferring muscle fiber nuclei type via linear matrix decomposition. This estimate was then compared with fiber type distribution measured by ATPase staining or myosin heavy chain protein isoform distribution of 62 muscle samples in two independent cohorts (n = 39 and 22). Results: The correlation between the sequencing-based method and the other two were rATPas = 0.44 [0.13–0.67], [95% CI], and rmyosin = 0.83 [0.61–0.93], with p = 5.70 × 10–3 and 2.00 × 10–6, respectively. The deconvolution inference of fiber type composition was accurate even for very low totRNAseq sequencing depths, i.e., down to an average of ~ 10,000 paired-end reads. Conclusions: This new method (https://github.com/OlaHanssonLab/PredictFiberType) consequently allows for measurement of fiber type distribution of a larger number of samples using totRNAseq in a cost and labor-efficient way. It is now feasible to study the association between fiber type distribution and e.g. health outcomes in large well-powered studies.

Subject headings

NATURVETENSKAP  -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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