Additional file 9 of Circular RNA expression and regulatory network prediction in posterior cingulate astrocytes in elderly subjects

Table S6. Donor demographics. (XLSX 41 kb

Additional file 3: of Circular RNA expression and regulatory network prediction in posterior cingulate astrocytes in elderly subjects

Figure S1. Circular-to-linear ratios. Ratio of average back-spliced reads to average linearly spliced reads for all detected circRNAs. (PDF 1075 kb

Additional file 7: of Circular RNA expression and regulatory network prediction in posterior cingulate astrocytes in elderly subjects

Figure S3. Computational workflow outline and filtering criterion. PC, posterior cingulate; RNAseq, RNA sequencing; circRNA, circular RNA; miRNA, microRNA; mRNA, messenger RNA. (PDF 928 kb

Additional file 1: of Circular RNA expression and regulatory network prediction in posterior cingulate astrocytes in elderly subjects

Table S1. Master summary of all detected circRNAs (XLSX 559 kb

Additional file 5: of Circular RNA expression and regulatory network prediction in posterior cingulate astrocytes in elderly subjects

Table S4 DESeq2 analysis results for genes with uncorrected P < 0.05, between AD and controls. (XLSX 229 kb

Additional file 2: of Circular RNA expression and regulatory network prediction in posterior cingulate astrocytes in elderly subjects

Table S2. Circular-to-linear ratios for all detected circRNAs (XLSX 342 kb

Additional file 10: of Circular RNA expression and regulatory network prediction in posterior cingulate astrocytes in elderly subjects

Table S7. Tool parameters used for circRNA detection in this study. (XLSX 45 kb

Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma

<div><p>Advanced cholangiocarcinoma continues to harbor a difficult prognosis and therapeutic options have been limited. During the course of a clinical trial of whole genomic sequencing seeking druggable targets, we examined six patients with advanced cholangiocarcinoma. Integrated genome-wide and whole transcriptome sequence analyses were performed on tumors from six patients with advanced, sporadic intrahepatic cholangiocarcinoma (SIC) to identify potential therapeutically actionable events. Among the somatic events captured in our analysis, we uncovered two novel therapeutically relevant genomic contexts that when acted upon, resulted in preliminary evidence of anti-tumor activity. Genome-wide structural analysis of sequence data revealed recurrent translocation events involving the <i>FGFR2</i> locus in three of six assessed patients. These observations and supporting evidence triggered the use of FGFR inhibitors in these patients. In one example, preliminary anti-tumor activity of pazopanib (<i>in vitro</i> FGFR2 IC₅₀≈350 nM) was noted in a patient with an <i>FGFR2-TACC3</i> fusion. After progression on pazopanib, the same patient also had stable disease on ponatinib, a pan-FGFR inhibitor (<i>in vitro</i>, FGFR2 IC₅₀≈8 nM). In an independent non-FGFR2 translocation patient, exome and transcriptome analysis revealed an allele specific somatic nonsense mutation (E384X) in <i>ERRFI1</i>, a direct negative regulator of <i>EGFR</i> activation. Rapid and robust disease regression was noted in this <i>ERRFI1</i> inactivated tumor when treated with erlotinib, an EGFR kinase inhibitor. <i>FGFR2</i> fusions and <i>ERRFI</i> mutations may represent novel targets in sporadic intrahepatic cholangiocarcinoma and trials should be characterized in larger cohorts of patients with these aberrations.</p></div

Fusion events.

<p>Fusion events.</p

Copy number changes and structural rearrangements.

<p>Whole genome data was utilized to determine copy number alterations and structural rearrangements in the genome for Patients 1–5. WGS was not conducted for patient 6. Red indicates copy number gain, green copy number loss and blue lines indicate structural rearrangements. Significant variability between samples was observed for both copy number changes and structural rearrangements. Patient 5 presented with numerous copy number changes and structural rearrangements contrasting with patient 4 who had minimal structural rearrangements and much smaller regions of copy number changes. Patient 3 is characterized by a large number of structural rearrangements with almost no copy number alterations; in contrast, Patient 1 has a moderate number of structural variations, but has large regions of copy number gain and loss. Patient 2 has a moderate number of structural rearrangements with multiple focal amplifications across the genome.</p