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Hood L.,Institute for Systems Biology | Friend S.H.,Sage Bionetworks
Nature Reviews Clinical Oncology | Year: 2011

Medicine will move from a reactive to a proactive discipline over the next decade-a discipline that is predictive, personalized, preventive and participatory (P4). P4 medicine will be fueled by systems approaches to disease, emerging technologies and analytical tools. There will be two major challenges to achieving P4 medicine-technical and societal barriers-and the societal barriers will prove the most challenging. How do we bring patients, physicians and members of the health-care community into alignment with the enormous opportunities of P4 medicine? In part, this will be done by the creation of new types of strategic partnerships-between patients, large clinical centers, consortia of clinical centers and patient-advocate groups. For some clinical trials it will necessary to recruit very large numbers of patients-and one powerful approach to this challenge is the crowd-sourced recruitment of patients by bringing large clinical centers together with patient-advocate groups. © 2011 Macmillan Publishers Limited. All rights reserved. Source

Wu C.,Tsinghua University | Zhu J.,Sage Bionetworks | Zhang X.,Tsinghua University
BMC Bioinformatics | Year: 2012

Background: To understand the roles they play in complex diseases, genes need to be investigated in the networks they are involved in. Integration of gene expression and network data is a promising approach to prioritize disease-associated genes. Some methods have been developed in this field, but the problem is still far from being solved.Results: In this paper, we developed a method, Networked Gene Prioritizer (NGP), to prioritize cancer-associated genes. Applications on several breast cancer and lung cancer datasets demonstrated that NGP performs better than the existing methods. It provides stable top ranking genes between independent datasets. The top-ranked genes by NGP are enriched in the cancer-associated pathways. The top-ranked genes by NGP-PLK1, MCM2, MCM3, MCM7, MCM10 and SKP2 might coordinate to promote cell cycle related processes in cancer but not normal cells.Conclusions: In this paper, we have developed a method named NGP, to prioritize cancer-associated genes. Our results demonstrated that NGP performs better than the existing methods. © 2012 Wu et al.; licensee BioMed Central Ltd. Source

In this paper we propose a vectorized implementation of the non-parametric bootstrap for statistics based on sample moments. Basically, we adopt the multinomial sampling formulation of the non-parametric bootstrap, and compute bootstrap replications of sample moment statistics by simply weighting the observed data according to multinomial counts instead of evaluating the statistic on a resampled version of the observed data. Using this formulation we can generate a matrix of bootstrap weights and compute the entire vector of bootstrap replications with a few matrix multiplications. Vectorization is particularly important for matrix-oriented programming languages such as R, where matrix/vector calculations tend to be faster than scalar operations implemented in a loop. We illustrate the application of the vectorized implementation in real and simulated data sets, when bootstrapping Pearson's sample correlation coefficient, and compared its performance against two state-of-the-art R implementations of the non-parametric bootstrap, as well as a straightforward one based on a for loop. Our investigations spanned varying sample sizes and number of bootstrap replications. The vectorized bootstrap compared favorably against the state-of-the-art implementations in all cases tested, and was remarkably/considerably faster for small/moderate sample sizes. The same results were observed in the comparison with the straightforward implementation, except for large sample sizes, where the vectorized bootstrap was slightly slower than the straightforward implementation due to increased time expenditures in the generation of weight matrices via multinomial sampling. © 2015 Elias Chaibub Neto. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source

Bountra C.,University of Oxford | Edwards A.M.,University of Toronto | Yamamoto K.R.,University of California at San Francisco | Friend S.H.,Sage Bionetworks
Science Translational Medicine | Year: 2011

Gloomy predictions about the future of pharma have forced the industry to investigate alternative models of drug discovery. Public-private partnerships (PPPs) have the potential to revitalize the discovery and development of first-in-class therapeutics. The new PPP Arch2POCM hopes to foster biomedical innovation through precompetitive validation of pioneer therapeutic targets for human diseases. In this meeting report, we capture insights garnered from the April 2011 Arch2POCM conference. Source

Hanzelmann S.,Hospital del Mar Medical Research Institute IMIM | Hanzelmann S.,University Pompeu Fabra | Castelo R.,Hospital del Mar Medical Research Institute IMIM | Castelo R.,University Pompeu Fabra | Guinney J.,Sage Bionetworks
BMC Bioinformatics | Year: 2013

Background: Gene set enrichment (GSE) analysis is a popular framework for condensing information from gene expression profiles into a pathway or signature summary. The strengths of this approach over single gene analysis include noise and dimension reduction, as well as greater biological interpretability. As molecular profiling experiments move beyond simple case-control studies, robust and flexible GSE methodologies are needed that can model pathway activity within highly heterogeneous data sets. Results: To address this challenge, we introduce Gene Set Variation Analysis (GSVA), a GSE method that estimates variation of pathway activity over a sample population in an unsupervised manner. We demonstrate the robustness of GSVA in a comparison with current state of the art sample-wise enrichment methods. Further, we provide examples of its utility in differential pathway activity and survival analysis. Lastly, we show how GSVA works analogously with data from both microarray and RNA-seq experiments. Conclusions: GSVA provides increased power to detect subtle pathway activity changes over a sample population in comparison to corresponding methods. While GSE methods are generally regarded as end points of a bioinformatic analysis, GSVA constitutes a starting point to build pathway-centric models of biology. Moreover, GSVA contributes to the current need of GSE methods for RNA-seq data. GSVA is an open source software package for R which forms part of the Bioconductor project and can be downloaded at http://www.bioconductor.org. © 2013 Hänzelmann et al.; licensee BioMed Central Ltd. Source

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