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Supplementary Table 2 - PDF file 58K, Comparison of baseline characteristics between patients of the EORTC26951 clinical trial that were included v. not included for genome wide methylation analysis

Purpose: Adequate preoperative staging of large sessile rectal tumors requires identifying adenomas that already contain an invasive focus, specifically those that are growing in or beyond the submucosa. We systematically compared chromosomal instability patterns in adenoma and carcinoma fractions of the same lesion to assess specific steps in rectal tumor progression.Experimental Design: We analyzed 36 formalin-fixed, paraffin-embedded tumors. Both the adenoma and carcinoma fractions were typed with single nucleotide polymorphism arrays and compared with 21 previously described pure adenomas. Eighteen cases were included in an intratumor heterogeneity analysis.Results: Five specific “malignant” events (gain of 8q, 13q, and 20q and loss of 17p and 18q) and aberrant staining for p53 and SMAD4 were all increased in the adenoma fractions of carcinoma cases compared with pure adenomas. Paired analysis revealed that 31% of the samples had an equal amount of malignant aberrations in their adenoma and carcinoma fractions, whereas 25% had one and 33% had two or more extra malignant events in the carcinoma fraction. Analysis of three core biopsies per patient showed a large degree of intratumor heterogeneity. However, the number of malignant aberrations in the biopsy with the most aberrations per tumor correlated with the corresponding adenoma or carcinoma fraction (r = 0.807; P < 0.001).Conclusion: Five specific chromosomal aberrations, combined with immunohistochemistry for p53 and SMAD4, can predict possible progression of sessile rectal adenomas to early rectal cancer and can, after validation studies, be added to preoperative staging. Preferably, three biopsies should be taken from each tumor to address intratumor heterogeneity.

Supplementary Table 3 - PDF file 61K, Molecular markers associated with methylation status

Supplementary Table from Progression and Tumor Heterogeneity Analysis in Early Rectal Cancer

Supplementary Table 4 - PDF file 69K, CpGs associated with benefit from adjuvant PCV chemotherapy

Supplementary Table 1 - PDF file 67K, Clinical and molecular characteristics of patients

Purpose: The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV treatment than others.Experimental Design: We conducted genome-wide methylation profiling of 115 samples included in the EORTC-26951 trial and extracted the CpG island hypermethylated phenotype (CIMP) and MGMT promoter methylation (MGMT-STP27) status.Results: We first show that methylation profiling can be conducted on archival tissues with a performance that is similar to snap-frozen tissue samples. We then conducted methylation profiling on EORTC-26951 clinical trial samples. Univariate analysis indicated that CIMP+ or MGMT-STP27 methylated tumors had an improved survival compared with CIMP− and/or MGMT-STP27 unmethylated tumors [median overall survival (OS), 1.05 vs. 6.46 years and 1.06 vs. 3.8 years, both P < 0.0001 for CIMP and MGMT-STP27 status, respectively]. Multivariable analysis indicates that CIMP and MGMT-STP27 are significant prognostic factors for survival in presence of age, sex, performance score, and review diagnosis in the model. CIMP+ and MGMT-STP27 methylated tumors showed a clear benefit from adjuvant PCV chemotherapy: the median OS of CIMP+ samples in the RT and RT-PCV arms was 3.27 and 9.51 years, respectively (P = 0.0033); for MGMT-STP27 methylated samples, it was 1.98 and 8.65 years. There was no such benefit for CIMP- or for MGMT-STP27 unmethylated tumors. MGMT-STP27 status remained significant in an interaction test (P = 0.003). Statistical analysis of microarray (SAM) identified 259 novel CpGs associated with treatment response.Conclusions:MGMT-STP27 may be used to guide treatment decisions in this tumor type. Clin Cancer Res; 19(19); 5513–22. ©2013 AACR.

Supplementary Figure 3 - PDF file 186K, SAM analysis of survival within CIMP+ or CIMP- tumors

Supplementary figure legends - PDF file 23K, Supplementary figure legends

Supplementary figure 1 - PDF file 810K, Comparison of baseline variables on Humanmethylation450 beadchips

Supplementary Figure 7 from Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than Histology

Supplementary Figure 5 from Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than Histology

Supplementary Figure 10 from Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than Histology

Supplementary Figure 6 from Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than Histology

Supplementary Figure 8 from Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than Histology

Supplementary Figure 3 from Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than Histology

Gliomas are the most common primary brain tumors with heterogeneous morphology and variable prognosis. Treatment decisions in patients rely mainly on histologic classification and clinical parameters. However, differences between histologic subclasses and grades are subtle, and classifying gliomas is subject to a large interobserver variability. To improve current classification standards, we have performed gene expression profiling on a large cohort of glioma samples of all histologic subtypes and grades. We identified seven distinct molecular subgroups that correlate with survival. These include two favorable prognostic subgroups (median survival, >4.7 years), two with intermediate prognosis (median survival, 1–4 years), two with poor prognosis (median survival

Supplementary Figure 2 from Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than Histology

Supplementary Figure 4 from Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than Histology

Supplementary Tables 1-6 from Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than Histology

Supplementary Figure 9 from Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than Histology

Supplementary Methods from Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than Histology

The receptive field (RF) of a visual neuron is the region of the space that elicits neuronal responses. It can be mapped using different techniques that allow inferring its spatial and temporal properties. Raw RF maps (RFmaps) are usually noisy, making it difficult to obtain and study important features of the RF. A possible solution is to smooth them using P-splines. Yet, raw RFmaps are characterized by sharp transitions in both space and time. Their analysis thus asks for spatiotemporal adaptive P-spline models, where smoothness can be locally adapted to the data. However, the literature lacks proposals for adaptive P-splines in more than two dimensions. Furthermore, the extra flexibility afforded by adaptive P-spline models is obtained at the cost of a high computational burden, especially in a multidimensional setting. To fill these gaps, this work presents a novel anisotropic locally adaptive P-spline model in two (e.g., space) and three (space and time) dimensions. Estimation is based on the recently proposed SOP (Separation of Overlapping Precision matrices) method, which provides the speed we look for. Besides the spatiotemporal analysis of the neuronal activity data that motivated this work, the practical performance of the proposal is evaluated through simulations, and comparisons with alternative methods are reported.

We present a fast and simple algorithm for super-resolution with single images. It is based on penalized least squares regression and exploits the tensor structure of two-dimensional convolution. A ridge penalty and a difference penalty are combined; the former removes singularities, while the latter eliminates ringing. We exploit the conjugate gradient algorithm to avoid explicit matrix inversion. Large images are handled with ease: zooming a 100 by 100 pixel image to 800 by 800 pixels takes less than a second on an average PC. Several examples, from applications in wide-field fluorescence microscopy, illustrate performance.

Summary: Alignment of peaks across samples is a difficult but unavoidable step in the data analysis for all analytical techniques containing a separation step like chromatography. Important application examples are the fields of metabolomics and proteomics. Parametric time warping (PTW) has already shown to be very useful in these fields because of the highly restricted form of the warping functions, avoiding overfitting. Here, we describe a new formulation of PTW, working on peak-picked features rather than on complete profiles. Not only does this allow for a much more smooth integration in existing pipelines, it also speeds up the (already among the fastest) algorithm by orders of magnitude. Using two publicly available datasets we show the potential of the new approach. The first set is a LC–DAD dataset of grape samples, and the second an LC–MS dataset of apple extracts. Availability and implementation: Parametric time warping of peak lists is implemented in the ptw package, version 1.9.1 and onwards, available from Github (https://github.com/rwehrens/ptw) and CRAN (http://cran.r-project.org). The package also contains a vignette, providing more theoretical details and scripts to reproduce the results below. Contact: ron.wehrens@wur.nl

Objective— Collateral artery development (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease, may be deregulated by vascular risk factors, eg, diabetes or hypercholesterolemia. Here, we compared the effects of either disturbed glucose metabolism or disturbed lipid metabolism on arteriogenesis. Methods and Results— Femoral artery occlusion was performed in streptozotocin(STZ)-treated mice, nonobese diabetic (NOD) mice, and insulin-resistant Ob/Ob mice on regular diet, and APOE3*Leiden mice on different hypercholesterolemic diets. Angiography and laser Doppler perfusion analysis of hindlimbs were performed postoperatively. Surprisingly, angiographic arteriogenesis was not impaired in diabetic and insulin-resistant mice. Perfusion recovery in STZ-treated and Ob/Ob mice was only decreased by 19% and 16%, respectively ( P P ≤0.01). Correspondingly, perfusion recovery was 41% decreased in APOE3*Leiden mice ( P P =0.02), but not with triglyceride, free fatty acid, glucose, or insulin levels. Conclusions— Hypercholesterolemia reduces arteriogenesis more dominantly than hyperglycemia or hyperinsulinemia in mice. This suggests that a disturbed lipid metabolism as observed in diabetic patients might be crucial for the impairment of collateral formation.