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The presence or absence alone of miRNA isoforms (isomiRs) successfully discriminate amongst the 32 TCGA cancer types

Aristeidis G. Telonis, Rogan Magee, Phillipe Loher, Inna Chervoneva, Eric Londin, Isidore Rigoutsos
doi: https://doi.org/10.1101/082685
Aristeidis G. Telonis
1Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Jefferson Alumni Hall #M81, Thomas Jefferson University, 1020 LocustStreet, Philadelphia, PA 19107.
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Rogan Magee
1Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Jefferson Alumni Hall #M81, Thomas Jefferson University, 1020 LocustStreet, Philadelphia, PA 19107.
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Phillipe Loher
1Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Jefferson Alumni Hall #M81, Thomas Jefferson University, 1020 LocustStreet, Philadelphia, PA 19107.
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Inna Chervoneva
2Division of Biostatistics, Thomas Jefferson University, Philadelphia, PA, USA
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Eric Londin
1Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Jefferson Alumni Hall #M81, Thomas Jefferson University, 1020 LocustStreet, Philadelphia, PA 19107.
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Isidore Rigoutsos
1Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Jefferson Alumni Hall #M81, Thomas Jefferson University, 1020 LocustStreet, Philadelphia, PA 19107.
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  • For correspondence: isidore.rigoutsos@jefferson.edu
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Abstract

Previously, we demonstrated that miRNA isoforms (isomiRs) are constitutive and their expression profiles depend on tissue, tissue state, and disease subtype. We have now extended our isomiR studies to The Cancer Genome Atlas (TCGA) repository. Specifically, we studied whether isomiR profiles can distinguish amongst the 32 cancers. We analyzed 10,271 datasets from 32 cancers and found 7,466 isomiRs from 807 miRNA hairpin-arms to be expressed above threshold. Using the top 20% most abundant isomiRs, we built a classifier that relied on “binary” isomiR profiles: isomiRs were simply represented as ‘present’ or ‘absent’ and, unlike previous methods, all knowledge about their expression levels was ignored. The classifier could label tumor samples with an average sensitivity of 93% and a False Discovery Rate of 3%. Notably, its ability to classify well persisted even when we reduced the set of used features (=isomiRs) by a factor of 10. A counterintuitive finding of our analysis is that the isomiRs and miRNA loci with the highest ability to classify tumors are not the ones that have been attracting the most research attention in the miRNA field. Our results provide a framework in which to study cancer-type-specific isomiRs and explore their potential uses as cancer biomarkers

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Posted October 24, 2016.
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The presence or absence alone of miRNA isoforms (isomiRs) successfully discriminate amongst the 32 TCGA cancer types
Aristeidis G. Telonis, Rogan Magee, Phillipe Loher, Inna Chervoneva, Eric Londin, Isidore Rigoutsos
bioRxiv 082685; doi: https://doi.org/10.1101/082685
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The presence or absence alone of miRNA isoforms (isomiRs) successfully discriminate amongst the 32 TCGA cancer types
Aristeidis G. Telonis, Rogan Magee, Phillipe Loher, Inna Chervoneva, Eric Londin, Isidore Rigoutsos
bioRxiv 082685; doi: https://doi.org/10.1101/082685

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