Integrative miRNA-mRNA analysis of BCP-ALL. (A) Workflow for the integrative miRNA-mRNA analysis of 111 BCP-ALL cases from the TARGET ALL cohort. (B-C) Dot plot showing the top enriched (B) Hallmark gene sets, and (C) Gene Ontology terms ranked according to gene ratio based on upregulated genes in sample pairs showing decreased miRNA expression and increased mRNA expression in the 111 BCP-ALL primary samples from the TARGET cohort. The adjusted P value is represented by the color scale, and the size of the dot reflects the number of genes assigned to the gene sets. Over-representation analysis was performed based on a 1-sided Fisher exact test conducted using the R package clusterProfiler. (D) Workflow for gene set enrichment analysis of genes significantly upregulated in relapse samples compared with primary samples from the 9 cases that acquired an MLC profile at relapse. (E) Dot plot showing the top enriched Hallmark gene sets, ranked according to the gene ratio of the upregulated genes shown in panel D. (F) Type and number of splicing alterations significantly associated with MLC compared with non-MLC cases in the TARGET cohort. The bars on the right denote alternative-splicing events that were increased in MLC cases. The bars on the left denote those that were decreased in MLC cases. (G) Venn diagram of decreased IR in the MLC compared with that in normal pro–B-cell and non-MLC samples, genes showing increased expression in the MLC compared with non-MLC samples, and genes with negatively correlated miRNA-mRNA pairs in MLC samples. (H) miR-30e-5p and MTA1 show inversely correlated expression patterns in 111 cases from the TARGET ALL cohort. Red dots represent MLC cases and blue dots represent non-MLC cases. (I) Heat map and clustering based on gene-set variation analysis enrichment scores for genes upregulated in normal B-precursor cells from 111 cases in the TARGET ALL cohort (left). Gene set enrichment analysis and enrichment plot for MLC and non-MLC cases, showing enrichment of genes upregulated in pre–B cells from MLC cases (right). CLP, common lymphoid progenitor; FDR, false discovery rate; FPKM, fragments per kilobase million; NES, normalized enrichment score; RPM, reads per million.

Integrative miRNA-mRNA analysis of BCP-ALL. (A) Workflow for the integrative miRNA-mRNA analysis of 111 BCP-ALL cases from the TARGET ALL cohort. (B-C) Dot plot showing the top enriched (B) Hallmark gene sets, and (C) Gene Ontology terms ranked according to gene ratio based on upregulated genes in sample pairs showing decreased miRNA expression and increased mRNA expression in the 111 BCP-ALL primary samples from the TARGET cohort. The adjusted P value is represented by the color scale, and the size of the dot reflects the number of genes assigned to the gene sets. Over-representation analysis was performed based on a 1-sided Fisher exact test conducted using the R package clusterProfiler. (D) Workflow for gene set enrichment analysis of genes significantly upregulated in relapse samples compared with primary samples from the 9 cases that acquired an MLC profile at relapse. (E) Dot plot showing the top enriched Hallmark gene sets, ranked according to the gene ratio of the upregulated genes shown in panel D. (F) Type and number of splicing alterations significantly associated with MLC compared with non-MLC cases in the TARGET cohort. The bars on the right denote alternative-splicing events that were increased in MLC cases. The bars on the left denote those that were decreased in MLC cases. (G) Venn diagram of decreased IR in the MLC compared with that in normal pro–B-cell and non-MLC samples, genes showing increased expression in the MLC compared with non-MLC samples, and genes with negatively correlated miRNA-mRNA pairs in MLC samples. (H) miR-30e-5p and MTA1 show inversely correlated expression patterns in 111 cases from the TARGET ALL cohort. Red dots represent MLC cases and blue dots represent non-MLC cases. (I) Heat map and clustering based on gene-set variation analysis enrichment scores for genes upregulated in normal B-precursor cells from 111 cases in the TARGET ALL cohort (left). Gene set enrichment analysis and enrichment plot for MLC and non-MLC cases, showing enrichment of genes upregulated in pre–B cells from MLC cases (right). CLP, common lymphoid progenitor; FDR, false discovery rate; FPKM, fragments per kilobase million; NES, normalized enrichment score; RPM, reads per million.

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