Ensemble Modeling Approach Targeting Heterogeneous RNA-Seq data: Application to Melanoma Pseudogenes

Abstract We studied the transcriptome landscape of skin cutaneous melanoma (SKCM) using 103 primary tumor samples from TCGA, and measured the expression levels of both protein coding genes and non-coding RNAs (ncRNAs). In particular, we emphasized pseudogenes potentially relevant to this cancer. While cataloguing the profiles based on the known biotypes, all the employed RNA-Seq methods generated just a small consensus of significant biotypes. We thus designed an approach to reconcile the profiles from all methods following a simple strategy: we selected genes that were confirmed as differentially expressed by the ensemble predictions obtained in a regression model. The main advantages of this approach are: 1) Selection of a high-confidence gene set identifying relevant pathways; 2) Use of a regression model whose covariates embed all method-driven outcomes to predict an averaged profile; 3) Method-specific assessment of prediction power and significance. Furthermore, the approach can be generalized to any biological system for which noisy RNA-Seq profiles are computed. As our analyses concerned bio-annotations of both high-quality protein coding genes and ncRNAs, we considered the associations between pseudogenes and parental genes (targets). Among the candidate targets that were validated, we identified PINK1, which is studied in patients with Parkinson and cancer (especially melanoma)

History of melanoma

Melanoma classically occurs in fair-skinned individuals of European origin. It is therefore surprising that the earliest evidence of melanoma has been found in the skeletons and skin of pre-Columbian, non-European mummies discovered in the foothills of the Peruvian Andes [1]. As well as widespread metastases in bone, rounded melanotic masses were identified in the skin of these mummies. Carbon dating has indicated that these individuals died around 2400 years ago

Hand transplantation: The state-of-the-art

The feasibility of hand transplantation has been demonstrated, both surgically and immunologically. Levels of immunosuppression comparable to regimens used in solid organ transplantation are proving sufficient to prevent graft loss. Many patients have achieved discriminative sensibility and recovery of intrinsic muscle function. In addition to restoration of function, hand transplantation offers considerable psychological benefits. The recipient's pre-operative psychological status, his motivation and his compliance with the intense rehabilitation programme are key issues. While the induction of graft specific tolerance represents a hope for the future, immunosuppression currently remains necessary and carries significant risks. Hand transplantation should, therefore, only be considered a therapeutic option for a carefully selected group of patients. © 2006 The British Society for Surgery of the Hand.SCOPUS: ar.jinfo:eu-repo/semantics/publishe