Figure 2.
lncRNA prioritization scheme and results. (A) The lncRNA prioritization scheme integrating results from the CRISPR-Cas9 screens, prognostic relevance of lncRNAs and their differential expression (DE) in patients with MM contrasted to normal tissues, from publicly available data sets. (B) CRISPR-Cas9 depletion log fold change (logFC) of individual nontargeting pgRNAs and pgRNAs targeting the top-priority hit RP11-350G8.5, across the 2 screens. The pgRNAs selected and used for the follow-up experimental validations are reported in red. (C) Association between high basal expression of RP11-350G8.5 and poorer overall (OS)/progression-free survival (PFS) in patients with MM (from the MMRF/coMMpass study). Reported P values are from a Cox proportional hazards regression model and from a Kaplan-Meier log-rank test performed across a partition induced by the best discriminating patient-percentile threshold of RP11-350G8.5 expression (40% and 31%, respectively, for OS and PFS), which was determined in a supervised manner, for visualization purposes. (D) Basal expression comparison for RP11-350G8.5 across patients with MM, normal tissues, healthy bone marrow, and plasma cells. In the prioritization pipeline, DE is computed via a generalized linear model. Here, for visualization purposes, a Student t test has been performed across groups and resulting P values are reported. (E) High-priority oncogenic lncRNAs outputted by the prioritization pipeline. Each point is an lncRNA with coordinates on the 2 axes indicating, respectively, best scaled -log transformed P values from 2 DE analyses comparing patients with MM with normal samples (x-axis), and priority scores (y-axis). Shapes indicate the cell line in which the lncRNAs were found significantly essential, according to the screen; color intensities are proportional to the best P value from OS/PSF based on the lncRNA expression observed in patients with MM. (F) Comparison of basal expression of RP11-350G8.5 (IL-6R-AS1) and its antisense gene (IL-6R) showing only a mild significant positive correlation between sense and antisense genes in each group of patients across groups of patients with MM segmented on the basis of their response to bortezomib treatment.

lncRNA prioritization scheme and results. (A) The lncRNA prioritization scheme integrating results from the CRISPR-Cas9 screens, prognostic relevance of lncRNAs and their differential expression (DE) in patients with MM contrasted to normal tissues, from publicly available data sets. (B) CRISPR-Cas9 depletion log fold change (logFC) of individual nontargeting pgRNAs and pgRNAs targeting the top-priority hit RP11-350G8.5, across the 2 screens. The pgRNAs selected and used for the follow-up experimental validations are reported in red. (C) Association between high basal expression of RP11-350G8.5 and poorer overall (OS)/progression-free survival (PFS) in patients with MM (from the MMRF/coMMpass study). Reported P values are from a Cox proportional hazards regression model and from a Kaplan-Meier log-rank test performed across a partition induced by the best discriminating patient-percentile threshold of RP11-350G8.5 expression (40% and 31%, respectively, for OS and PFS), which was determined in a supervised manner, for visualization purposes. (D) Basal expression comparison for RP11-350G8.5 across patients with MM, normal tissues, healthy bone marrow, and plasma cells. In the prioritization pipeline, DE is computed via a generalized linear model. Here, for visualization purposes, a Student t test has been performed across groups and resulting P values are reported. (E) High-priority oncogenic lncRNAs outputted by the prioritization pipeline. Each point is an lncRNA with coordinates on the 2 axes indicating, respectively, best scaled -log transformed P values from 2 DE analyses comparing patients with MM with normal samples (x-axis), and priority scores (y-axis). Shapes indicate the cell line in which the lncRNAs were found significantly essential, according to the screen; color intensities are proportional to the best P value from OS/PSF based on the lncRNA expression observed in patients with MM. (F) Comparison of basal expression of RP11-350G8.5 (IL-6R-AS1) and its antisense gene (IL-6R) showing only a mild significant positive correlation between sense and antisense genes in each group of patients across groups of patients with MM segmented on the basis of their response to bortezomib treatment.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal