Novel risk genes for systemic lupus erythematosus predicted by random forest classification
Abstract Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual’s SLE risk we designed a random forest classifier using SNP genotype data generate...
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oai:doaj.org-article:95b05eb647a546ff93ea49bf8605180e2021-12-02T11:52:17ZNovel risk genes for systemic lupus erythematosus predicted by random forest classification10.1038/s41598-017-06516-12045-2322https://doaj.org/article/95b05eb647a546ff93ea49bf8605180e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06516-1https://doaj.org/toc/2045-2322Abstract Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual’s SLE risk we designed a random forest classifier using SNP genotype data generated on the “Immunochip” from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells.Jonas Carlsson AlmlöfAndrei AlexssonJuliana Imgenberg-KreuzLina SylwanChristofer BäcklinDag LeonardGunnel NordmarkKarolina TandreMaija-Leena ElorantaLeonid PadyukovChristine BengtssonAndreas JönsenSolbritt Rantapää DahlqvistChristopher SjöwallAnders A. BengtssonIva GunnarssonElisabet SvenungssonLars RönnblomJohanna K. SandlingAnn-Christine SyvänenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Jonas Carlsson Almlöf Andrei Alexsson Juliana Imgenberg-Kreuz Lina Sylwan Christofer Bäcklin Dag Leonard Gunnel Nordmark Karolina Tandre Maija-Leena Eloranta Leonid Padyukov Christine Bengtsson Andreas Jönsen Solbritt Rantapää Dahlqvist Christopher Sjöwall Anders A. Bengtsson Iva Gunnarsson Elisabet Svenungsson Lars Rönnblom Johanna K. Sandling Ann-Christine Syvänen Novel risk genes for systemic lupus erythematosus predicted by random forest classification |
| description |
Abstract Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual’s SLE risk we designed a random forest classifier using SNP genotype data generated on the “Immunochip” from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells. |
| format |
article |
| author |
Jonas Carlsson Almlöf Andrei Alexsson Juliana Imgenberg-Kreuz Lina Sylwan Christofer Bäcklin Dag Leonard Gunnel Nordmark Karolina Tandre Maija-Leena Eloranta Leonid Padyukov Christine Bengtsson Andreas Jönsen Solbritt Rantapää Dahlqvist Christopher Sjöwall Anders A. Bengtsson Iva Gunnarsson Elisabet Svenungsson Lars Rönnblom Johanna K. Sandling Ann-Christine Syvänen |
| author_facet |
Jonas Carlsson Almlöf Andrei Alexsson Juliana Imgenberg-Kreuz Lina Sylwan Christofer Bäcklin Dag Leonard Gunnel Nordmark Karolina Tandre Maija-Leena Eloranta Leonid Padyukov Christine Bengtsson Andreas Jönsen Solbritt Rantapää Dahlqvist Christopher Sjöwall Anders A. Bengtsson Iva Gunnarsson Elisabet Svenungsson Lars Rönnblom Johanna K. Sandling Ann-Christine Syvänen |
| author_sort |
Jonas Carlsson Almlöf |
| title |
Novel risk genes for systemic lupus erythematosus predicted by random forest classification |
| title_short |
Novel risk genes for systemic lupus erythematosus predicted by random forest classification |
| title_full |
Novel risk genes for systemic lupus erythematosus predicted by random forest classification |
| title_fullStr |
Novel risk genes for systemic lupus erythematosus predicted by random forest classification |
| title_full_unstemmed |
Novel risk genes for systemic lupus erythematosus predicted by random forest classification |
| title_sort |
novel risk genes for systemic lupus erythematosus predicted by random forest classification |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/95b05eb647a546ff93ea49bf8605180e |
| work_keys_str_mv |
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| _version_ |
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