Clinicopathologic characteristics with different BRCA1/2 status.

<p>For categorical data (Tumor stage and grade, residual tumor size, response to chemotherapy therapy and platinum status), the Fisher exact test was used to calculate P value in <i>R</i>; for continuous variable such as age, the Wilcoxon rank sum test was used in <i>R</i>. Patients with debulking status “no macroscopic disease” are labeled as 0 cm in residual tumor size. Number (NO.) depicts the corresponding number of patients in each category. Missing values are excluded from the test analyses. BRCA wild-type cases do not include the BRCA1 methylation cases.</p><p>Clinicopathologic characteristics with different BRCA1/2 status.</p

Cox proportional hazard model using relevant pretreatment factors for patients with different BRCA1/2 mutation status.

<p>Abbreviations: High/Low BRCA, BRCA mutation cases in high/low level group of mutations, CNCs or scores; HR, hazard ratio; CI, confidence interval; Debulking, residual tumor size.</p><p>Two-sided <i>P</i> values were calculated using Cox regression model adjusting for all the variables in the table.</p><p>Patients with debulking status “no macroscopic disease” are labeled as 0 cm.</p><p>Cox proportional hazard model using relevant pretreatment factors for patients with different BRCA1/2 mutation status.</p

Association of genomic instability with <i>BRCA1/2</i> mutations and survival in ovarian cancer.

<p>(<b>A</b>) Both <i>BRCA1</i> and <i>BRCA2</i> mutated tumors show elevated level genome mutations. High mutation group of <i>BRCA1/2</i> mutated ovarian cancer patients shows significantly improved survival than wild-type patients, whereas low mutation group of <i>BRCA1/2</i> mutated patients shows nonsignificant difference compared with wild-type patients. (<b>B</b>) Both <i>BRCA1</i> and <i>BRCA2</i> mutated tumors show increased copy number changes. High CNCs group of <i>BRCA1/2</i> mutated ovarian cancer patients shows significantly improved survival than wild-type patients, whereas low CNCs group shows nonsignificant difference compared with wild-type patients. (<b>C</b>) Both <i>BRCA1</i> and <i>BRCA2</i> mutated patients show increased genomic instability score, with <i>BRCA2</i> mutated patients show higher score distribution than <i>BRCA1</i> mutated patients. High scoring group of <i>BRCA1/2</i> mutated patients shows significantly improved survival than wild-type patients, whereas low scoring group shows nonsignificant difference compared with wild-type patients.</p

Association of high vs low scoring subgroup with clinical characteristics.

<p>Association of high vs low scoring subgroup with clinical characteristics.</p

Association of the genomic instability score with HR-deficiency and platinum-response in ovarian cancer.

<p>(<b>A</b>) The distribution of score in <i>BRCA1</i> hyper-methylated patients is significantly higher than that in <i>BRCA</i> wild-type patients. (<b>B</b>) The distribution of score in HR-deficient patients (including <i>EMSY</i> amplification cases, and <i>PTEN</i>, Fanconi Anemia genes, <i>RAD</i> genes, <i>ATM</i>, <i>ATR</i> and <i>CHEK1/2</i> deficient cases) is significantly higher than that in other <i>BRCA</i> wild-type patients. (<b>C</b>) Association of the score with complete response (CR). The scores of all patients (n = 325) were divided into 12 equal intervals. The percentage of patients achieving a CR (according to the Response Evaluation Criteria in Solid Tumors) was calculated for patients in each interval and was plotted against each scoring interval in increasing order. Patients in high scoring interval show increasing likelihood of achieving CR. The dashed line represents linear regression line through the data points. (<b>D</b>) Same as (<b>C</b>) but calculating for platinum-status. 133 platinum-sensitive patients and 62 platinum-resistant patients were analyzed.</p

Association of <i>BRCA1</i> and <i>BRCA2</i> mutations with overall survival (A) and Progression-free survival (B) in ovarian cancer.

<p>Association of <i>BRCA1</i> and <i>BRCA2</i> mutations with overall survival (A) and Progression-free survival (B) in ovarian cancer.</p

Additional file 1: of A potential signature of eight long non-coding RNAs predicts survival in patients with non-small cell lung cancer

Figure S1. The boxplot of expression level of eight prognostic lncRNAs in lung cancer and control samples

The state of the sub-networks in response to hydrogen peroxide in segregants inherited alleles from RM and BY.

<p>Solid edges indicate correlated expression between proteins in one allele state, whereas that organization is lost in another allele state (dotted line). Edge colors represent diverse interaction types between proteins, whereas node colors represent changes in gene expression between wild and mutant groups; green denotes down-regulation and red denotes up-regulation. Triangle nodes present genes annotated in ‘ergosterol metabolic process’, ‘lipid biosynthetic process’, and ‘oxidation reduction’. Nodes with dark edges are known drug targets of hydrogen peroxide based on Stitch2 database.</p

The QTLs distribution and drug targets enrichment of SMPs.

<p>(A) The QTLs distribution along the whole genome for 53 small-molecule drugs. QTLs associated with different SMPs are marked with various colors. (B) The sub-networks responding to the SMP response of hydrogen peroxide and menadione. Red nodes are known drug targets included in the STITCH database.</p

The changing pattern of molecular networks under allele-specific context determined by LD blocks.

<p>(A) Hierarchical clustering on the perturbed interactions based on the association matrix between blocks and their perturbing interactions in PPI, PDI, KPI, and EEI networks, respectively, in which rows represent blocks and columns represent interactions. In each of the four sub-matrices, blocks associated with less than ten interactions are filtered out. The columns are reordered according to hierarchical clustering. The rows colored correspond to B20. (B) The allele-specific sub-network associated with B20. The sub-network is composed of 142 PPIs, 54 PDIs, 93 KPIs, and 26 EEIs, which are marked with green, red, blue and orange, respectively. Nodes marked with red are proteins constituting a GO cellular component (nuclear lumen), and PPIs among these genes are regulated by B20. Nodes marked with green are enzymes from a KEGG pathway (DNA-directed RNA polymerase activity), and their EEIs are regulated by B20.</p