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159 results on '"Carlin, Daniel"'

1. Schr\'odinger's Cheshire Cat: A tabletop experiment to measure the Di\'osi-Penrose collapse time and demonstrate Objective Reduction (OR)

Author

Tagg, James, Reid, William, and Carlin, Daniel

Subjects
Quantum Physics, General Relativity and Quantum Cosmology
Abstract

For nearly 100 years, the paradox of Schr\"odinger's Cat has remained unresolved. Why does the world we live in appear classical despite being composed of quantum particles governed by the Schr\"odinger wave equation? Lajos Di\'osi and Roger Penrose propose the wavefunction collapses because it describes two incompatible space-times, demonstrating an inconsistency between quantum mechanics and general relativity. To avoid this paradox, collapse must occur within Heisenberg's time-energy uncertainty limit. Subatomic particles with low mass, and correspondingly low energy, collapse in years, while superposed cats would collapse almost instantaneously. We propose a table-top experiment to put two small mirrors into superposition and observe them collapse in a time consistent with the Di\'osi-Penrose model. We employ two techniques to perform this experiment in ambient laboratory conditions. Most experiments separate a small mass by a large distance. In contrast, we displace a large mass by a small distance where the self-energy follows an inverse square law with correspondingly high collapse times. We further use a symmetrical apparatus, where a break in symmetry indicates collapse independent of decoherence., Comment: 5 pages, 3 figures

Published
2024

2. Spatially organized cellular communities form the developing human heart.

Author

Lu, Ting-Yu, Ma, Qixuan, Tran, Shaina, Zhang, Bo, Carlin, Daniel, Monell, Alexander, Blair, Andrew, Wang, Zilu, Eschbach, Jacqueline, Li, Bin, Destici, Eugin, Ren, Bing, Evans, Sylvia, Chen, Shaochen, Zhu, Quan, Chi, Neil, Hu, Robert, Kern, Colin, Zhang, Qingquan, and Farah, Elie

Subjects
Animals, Humans, Mice, Heart, Heart Diseases, Heart Ventricles, In Situ Hybridization, Fluorescence, Models, Animal, Myocardium, Myocytes, Cardiac, Single-Cell Gene Expression Analysis, Body Patterning
Abstract

The heart, which is the first organ to develop, is highly dependent on its form to function1,2. However, how diverse cardiac cell types spatially coordinate to create the complex morphological structures that are crucial for heart function remains unclear. Here we integrated single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization to resolve the identity of the cardiac cell types that develop the human heart. This approach also provided a spatial mapping of individual cells that enables illumination of their organization into cellular communities that form distinct cardiac structures. We discovered that many of these cardiac cell types further specified into subpopulations exclusive to specific communities, which support their specialization according to the cellular ecosystem and anatomical region. In particular, ventricular cardiomyocyte subpopulations displayed an unexpected complex laminar organization across the ventricular wall and formed, with other cell subpopulations, several cellular communities. Interrogating cell-cell interactions within these communities using in vivo conditional genetic mouse models and in vitro human pluripotent stem cell systems revealed multicellular signalling pathways that orchestrate the spatial organization of cardiac cell subpopulations during ventricular wall morphogenesis. These detailed findings into the cellular social interactions and specialization of cardiac cell types constructing and remodelling the human heart offer new insights into structural heart diseases and the engineering of complex multicellular tissues for human heart repair.

Published
2024

3. Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer’s disease

Author

Whittaker, Daniel S, Akhmetova, Laila, Carlin, Daniel, Romero, Haylie, Welsh, David K, Colwell, Christopher S, and Desplats, Paula

Subjects
Biochemistry and Cell Biology, Biological Sciences, Clinical Research, Acquired Cognitive Impairment, Nutrition, Alzheimer's Disease, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Neurodegenerative, Sleep Research, Dementia, Behavioral and Social Science, Aging, 2.1 Biological and endogenous factors, Neurological, Mice, Animals, Humans, Alzheimer Disease, Mice, Transgenic, Disease Models, Animal, Circadian Rhythm, Brain, Amyloid beta-Peptides, Alzheimer's mouse models, Alzheimer’s disease, amyloid plaque deposition, circadian rhythms, cognition, hippocampal transcriptome, memory, neuroinflammation, rhythmic transcription, time-restricted feeding, Medical Biochemistry and Metabolomics, Endocrinology & Metabolism, Biochemistry and cell biology, Medical biochemistry and metabolomics
Abstract

Circadian disruptions impact nearly all people with Alzheimer's disease (AD), emphasizing both their potential role in pathology and the critical need to investigate the therapeutic potential of circadian-modulating interventions. Here, we show that time-restricted feeding (TRF) without caloric restriction improved key disease components including behavioral timing, disease pathology, hippocampal transcription, and memory in two transgenic (TG) mouse models of AD. We found that TRF had the remarkable capability of simultaneously reducing amyloid deposition, increasing Aβ42 clearance, improving sleep and memory, and normalizing daily transcription patterns of multiple genes, including those associated with AD and neuroinflammation. Thus, our study unveils for the first time the pleiotropic nature of timed feeding on AD, which has far-reaching effects beyond metabolism, ameliorating neurodegeneration and the misalignment of circadian rhythmicity. Since TRF can substantially modify disease trajectory, this intervention has immediate translational potential, addressing the urgent demand for accessible approaches to reduce or halt AD progression.

Published
2023

5. Strategies for Network GWAS Evaluated Using Classroom Crowd Science.

Author

Fong, Samson H, Carlin, Daniel E, Ozturk, Kivilcim, 2018 UCSD Network Biology Class, and Ideker, Trey

Subjects
UCSD Network Biology Class, Humans, Computational Biology, Education, Graduate, Genome-Wide Association Study, Crowdsourcing, Genetics, Bioengineering, Human Genome, Biochemistry and Cell Biology
Abstract

Biological networks can substantially boost power to identify disease genes in genome-wide association studies. To explore different network GWAS methods, we challenged students of a UC San Diego graduate level bioinformatics course, Network Biology and Biomedicine, to explore and improve such algorithms during a four-week-long classroom competition. Here, we report the many creative solutions and share our experiences in conducting classroom crowd science as both a research and pedagogical tool.

Published
2019

6. The Emerging Potential for Network Analysis to Inform Precision Cancer Medicine

Author

Ozturk, Kivilcim, Dow, Michelle, Carlin, Daniel E, Bejar, Rafael, and Carter, Hannah

Subjects
Biological Sciences, Genetics, Cancer, Human Genome, Rare Diseases, Hematology, Good Health and Well Being, Algorithms, Disease Susceptibility, Genomics, Humans, Medical Oncology, Neoplasms, Neural Networks, Computer, Precision Medicine, Prognosis, Systems Biology, cancer systems biology, precision cancer medicine, network analysis, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Microbiology, Biochemistry & Molecular Biology, Biochemistry and cell biology
Abstract

Precision cancer medicine promises to tailor clinical decisions to patients using genomic information. Indeed, successes of drugs targeting genetic alterations in tumors, such as imatinib that targets BCR-ABL in chronic myelogenous leukemia, have demonstrated the power of this approach. However, biological systems are complex, and patients may differ not only by the specific genetic alterations in their tumor, but also by more subtle interactions among such alterations. Systems biology and more specifically, network analysis, provides a framework for advancing precision medicine beyond clinical actionability of individual mutations. Here we discuss applications of network analysis to study tumor biology, early methods for N-of-1 tumor genome analysis, and the path for such tools to the clinic.

Published
2018

7. Systematic Evaluation of Molecular Networks for Discovery of Disease Genes

Author

Huang, Justin K, Carlin, Daniel E, Yu, Michael Ku, Zhang, Wei, Kreisberg, Jason F, Tamayo, Pablo, and Ideker, Trey

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Biotechnology, Algorithms, Computational Biology, Gene Regulatory Networks, Genetic Predisposition to Disease, Genome, Human, Humans, genome-wide disease association, molecular networks, network analysis, network propagation, Biochemistry and Cell Biology, Biochemistry and cell biology
Abstract

Gene networks are rapidly growing in size and number, raising the question of which networks are most appropriate for particular applications. Here, we evaluate 21 human genome-wide interaction networks for their ability to recover 446 disease gene sets identified through literature curation, gene expression profiling, or genome-wide association studies. While all networks have some ability to recover disease genes, we observe a wide range of performance with STRING, ConsensusPathDB, and GIANT networks having the best performance overall. A general tendency is that performance scales with network size, suggesting that new interaction discovery currently outweighs the detrimental effects of false positives. Correcting for size, we find that the DIP network provides the highest efficiency (value per interaction). Based on these results, we create a parsimonious composite network with both high efficiency and performance. This work provides a benchmark for selection of molecular networks in human disease research.

Published
2018

8. A Community Challenge for Inferring Genetic Predictors of Gene Essentialities through Analysis of a Functional Screen of Cancer Cell Lines

Author

Gönen, Mehmet, Weir, Barbara A, Cowley, Glenn S, Vazquez, Francisca, Guan, Yuanfang, Jaiswal, Alok, Karasuyama, Masayuki, Uzunangelov, Vladislav, Wang, Tao, Tsherniak, Aviad, Howell, Sara, Marbach, Daniel, Hoff, Bruce, Norman, Thea C, Airola, Antti, Bivol, Adrian, Bunte, Kerstin, Carlin, Daniel, Chopra, Sahil, Deran, Alden, Ellrott, Kyle, Gopalacharyulu, Peddinti, Graim, Kiley, Kaski, Samuel, Khan, Suleiman A, Newton, Yulia, Ng, Sam, Pahikkala, Tapio, Paull, Evan, Sokolov, Artem, Tang, Hao, Tang, Jing, Wennerberg, Krister, Xie, Yang, Zhan, Xiaowei, Zhu, Fan, Community, Broad-DREAM, Afsari, Bahman, Aittokallio, Tero, Boehm, Jesse S, Chang, Yu-Chuan, Chen, Tenghui, Chong, Zechen, Elmarakeby, Haitham, Fertig, Elana J, Gonçalves, Emanuel, Gong, Pinghua, Hafemeister, Christoph, Hahn, William C, Heath, Lenwood, Kędziorski, Łukasz, Khemka, Niraj, King, Erh-kan, Lauria, Mario, Liu, Mark, Machado, Daniel, Mamitsuka, Hiroshi, Margolin, Adam A, Mazurkiewicz, Mateusz, Menden, Michael P, Migacz, Szymon, Nie, Zhi, Praveen, Paurush, Priami, Corrado, Rizzetto, Simone, Rocha, Miguel, Root, David E, Rudd, Cameron, Rudnicki, Witold R, Saez-Rodriguez, Julio, Song, Lei, Stolovitzky, Gustavo, Stuart, Joshua M, Sun, Duanchen, and Szalai, Bence

Subjects
Biological Sciences, Genetics, Biotechnology, Prevention, Cancer, Human Genome, Algorithms, Cell Line, Tumor, Gene Expression, Genes, Essential, Genomics, Humans, RNA, Small Interfering, Broad-DREAM Community, cancer genomics, community challenge, crowdsourcing, functional screen, machine learning, oncogene, Biochemistry and Cell Biology, Biochemistry and cell biology
Abstract

We report the results of a DREAM challenge designed to predict relative genetic essentialities based on a novel dataset testing 98,000 shRNAs against 149 molecularly characterized cancer cell lines. We analyzed the results of over 3,000 submissions over a period of 4 months. We found that algorithms combining essentiality data across multiple genes demonstrated increased accuracy; gene expression was the most informative molecular data type; the identity of the gene being predicted was far more important than the modeling strategy; well-predicted genes and selected molecular features showed enrichment in functional categories; and frequently selected expression features correlated with survival in primary tumors. This study establishes benchmarks for gene essentiality prediction, presents a community resource for future comparison with this benchmark, and provides insights into factors influencing the ability to predict gene essentiality from functional genetic screens. This study also demonstrates the value of releasing pre-publication data publicly to engage the community in an open research collaboration.

Published
2017

9. Modeling of RAS complexes supports roles in cancer for less studied partners

Author

Engin, H Billur, Carlin, Daniel, Pratt, Dexter, and Carter, Hannah

Subjects
Biochemistry and Cell Biology, Bioinformatics and Computational Biology, Biological Sciences, Cancer, Aetiology, 2.1 Biological and endogenous factors, RAS, Hypervariable region, Allosteric region, Effector lobe, Protein-protein interaction, Protein interaction interface, Protein structure, Tumor suppressor interaction
Abstract

BackgroundRAS protein interactions have predominantly been studied in the context of the RAF and PI3kinase oncogenic pathways. Structural modeling and X-ray crystallography have demonstrated that RAS isoforms bind to canonical downstream effector proteins in these pathways using the highly conserved switch I and II regions. Other non-canonical RAS protein interactions have been experimentally identified, however it is not clear whether these proteins also interact with RAS via the switch regions.ResultsTo address this question we constructed a RAS isoform-specific protein-protein interaction network and predicted 3D complexes involving RAS isoforms and interaction partners to identify the most probable interaction interfaces. The resulting models correctly captured the binding interfaces for well-studied effectors, and additionally implicated residues in the allosteric and hyper-variable regions of RAS proteins as the predominant binding site for non-canonical effectors. Several partners binding to this new interface (SRC, LGALS1, RABGEF1, CALM and RARRES3) have been implicated as important regulators of oncogenic RAS signaling. We further used these models to investigate competitive binding and multi-protein complexes compatible with RAS surface occupancy and the putative effects of somatic mutations on RAS protein interactions.ConclusionsWe discuss our findings in the context of RAS localization to the plasma membrane versus within the cytoplasm and provide a list of RAS protein interactions with possible cancer-related consequences, which could help guide future therapeutic strategies to target RAS proteins.

Published
2017

10. Prophetic Granger Causality to infer gene regulatory networks

Author

Carlin, Daniel E, Paull, Evan O, Graim, Kiley, Wong, Christopher K, Bivol, Adrian, Ryabinin, Peter, Ellrott, Kyle, Sokolov, Artem, and Stuart, Joshua M

Subjects
Biochemistry and Cell Biology, Bioinformatics and Computational Biology, Biological Sciences, Cancer, Bioengineering, Biotechnology, Genetics, Causality, Computational Biology, Gene Regulatory Networks, Humans, Machine Learning, Models, Theoretical, Neoplasms, Systems Biology, General Science & Technology
Abstract

We introduce a novel method called Prophetic Granger Causality (PGC) for inferring gene regulatory networks (GRNs) from protein-level time series data. The method uses an L1-penalized regression adaptation of Granger Causality to model protein levels as a function of time, stimuli, and other perturbations. When combined with a data-independent network prior, the framework outperformed all other methods submitted to the HPN-DREAM 8 breast cancer network inference challenge. Our investigations reveal that PGC provides complementary information to other approaches, raising the performance of ensemble learners, while on its own achieves moderate performance. Thus, PGC serves as a valuable new tool in the bioinformatics toolkit for analyzing temporal datasets. We investigate the general and cell-specific interactions predicted by our method and find several novel interactions, demonstrating the utility of the approach in charting new tumor wiring.

Published
2017

11. Inferring causal molecular networks: empirical assessment through a community-based effort

Author

Hill, Steven M., Heiser, Laura M., Cokelaer, Thomas, Unger, Michael, Nesser, Nicole K., Carlin, Daniel E., Zhang, Yang, Sokolov, Artem, Paull, Evan O., Wong, Chris K., Graim, Kiley, Bivol, Adrian, Wang, Haizhou, Zhu, Fan, Afsari, Bahman, Danilova, Ludmila V., Favorov, Alexander V., Lee, Wai Shing, Taylor, Dane, Hu, Chenyue W., Long, Byron L., Noren, David P., Bisberg, Alexander J., Mills, Gordon B., Gray, Joe W., Kellen, Michael, Norman, Thea, Friend, Stephen, Qutub, Amina A., Fertig, Elana J., Guan, Yuanfang, Song, Mingzhou, Stuart, Joshua M., Spellman, Paul T., Koeppl, Heinz, Stolovitzky, Gustavo, Saez-Rodriguez, Julio, Mukherjee, Sach, Hill, Steven M., Heiser, Laura M., Cokelaer, Thomas, Unger, Michael, Nesser, Nicole K., Carlin, Daniel E., Zhang, Yang, Sokolov, Artem, Paull, Evan O., Wong, Chris K., Graim, Kiley, Bivol, Adrian, Wang, Haizhou, Zhu, Fan, Afsari, Bahman, Danilova, Ludmila V., Favorov, Alexander V., Lee, Wai Shing, Taylor, Dane, Hu, Chenyue W., Long, Byron L., Noren, David P., Bisberg, Alexander J., Mills, Gordon B., Gray, Joe W., Kellen, Michael, Norman, Thea, Friend, Stephen, Qutub, Amina A., Fertig, Elana J., Guan, Yuanfang, Song, Mingzhou, Stuart, Joshua M., Spellman, Paul T., Koeppl, Heinz, Stolovitzky, Gustavo, Saez-Rodriguez, Julio, and Mukherjee, Sach

Abstract

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense.

Published
2024

12. Phosphoproteome Integration Reveals Patient-Specific Networks in Prostate Cancer.

Author

Drake, Justin M, Paull, Evan O, Graham, Nicholas A, Lee, John K, Smith, Bryan A, Titz, Bjoern, Stoyanova, Tanya, Faltermeier, Claire M, Uzunangelov, Vladislav, Carlin, Daniel E, Fleming, Daniel Teo, Wong, Christopher K, Newton, Yulia, Sudha, Sud, Vashisht, Ajay A, Huang, Jiaoti, Wohlschlegel, James A, Graeber, Thomas G, Witte, Owen N, and Stuart, Joshua M

Subjects
Humans, Phosphoproteins, Proteome, Signal Transduction, Algorithms, Male, Transcriptome, Prostatic Neoplasms, Castration-Resistant, Precision Medicine, Prostatic Neoplasms, Castration-Resistant, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

We used clinical tissue from lethal metastatic castration-resistant prostate cancer (CRPC) patients obtained at rapid autopsy to evaluate diverse genomic, transcriptomic, and phosphoproteomic datasets for pathway analysis. Using Tied Diffusion through Interacting Events (TieDIE), we integrated differentially expressed master transcriptional regulators, functionally mutated genes, and differentially activated kinases in CRPC tissues to synthesize a robust signaling network consisting of druggable kinase pathways. Using MSigDB hallmark gene sets, six major signaling pathways with phosphorylation of several key residues were significantly enriched in CRPC tumors after incorporation of phosphoproteomic data. Individual autopsy profiles developed using these hallmarks revealed clinically relevant pathway information potentially suitable for patient stratification and targeted therapies in late stage prostate cancer. Here, we describe phosphorylation-based cancer hallmarks using integrated personalized signatures (pCHIPS) that shed light on the diversity of activated signaling pathways in metastatic CRPC while providing an integrative, pathway-based reference for drug prioritization in individual patients.

Published
2016

13. Inferring causal molecular networks: empirical assessment through a community-based effort

Author

Hill, Steven M, Heiser, Laura M, Cokelaer, Thomas, Unger, Michael, Nesser, Nicole K, Carlin, Daniel E, Zhang, Yang, Sokolov, Artem, Paull, Evan O, Wong, Chris K, Graim, Kiley, Bivol, Adrian, Wang, Haizhou, Zhu, Fan, Afsari, Bahman, Danilova, Ludmila V, Favorov, Alexander V, Lee, Wai Shing, Taylor, Dane, Hu, Chenyue W, Long, Byron L, Noren, David P, Bisberg, Alexander J, Mills, Gordon B, Gray, Joe W, Kellen, Michael, Norman, Thea, Friend, Stephen, Qutub, Amina A, Fertig, Elana J, Guan, Yuanfang, Song, Mingzhou, Stuart, Joshua M, Spellman, Paul T, Koeppl, Heinz, Stolovitzky, Gustavo, Saez-Rodriguez, Julio, and Mukherjee, Sach

Subjects
Biochemistry and Cell Biology, Biological Sciences, Networking and Information Technology R&D (NITRD), Bioengineering, Cancer, 2.1 Biological and endogenous factors, Generic health relevance, Algorithms, Causality, Computational Biology, Computer Simulation, Gene Expression Profiling, Gene Regulatory Networks, Humans, Models, Biological, Neoplasms, Protein Interaction Mapping, Signal Transduction, Software, Systems Biology, Tumor Cells, Cultured, HPN-DREAM Consortium, Technology, Medical and Health Sciences, Developmental Biology, Biological sciences
Abstract

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense.

Published
2016

14. Pathway-Based Genomics Prediction using Generalized Elastic Net.

Author

Sokolov, Artem, Carlin, Daniel E, Paull, Evan O, Baertsch, Robert, and Stuart, Joshua M

Subjects
Animals, Humans, Proteome, Chromosome Mapping, Protein Interaction Mapping, Signal Transduction, Models, Genetic, Computer Simulation, Pattern Recognition, Automated, Models, Genetic, Pattern Recognition, Automated, Mathematical Sciences, Biological Sciences, Information and Computing Sciences, Bioinformatics
Abstract

We present a novel regularization scheme called The Generalized Elastic Net (GELnet) that incorporates gene pathway information into feature selection. The proposed formulation is applicable to a wide variety of problems in which the interpretation of predictive features using known molecular interactions is desired. The method naturally steers solutions toward sets of mechanistically interlinked genes. Using experiments on synthetic data, we demonstrate that pathway-guided results maintain, and often improve, the accuracy of predictors even in cases where the full gene network is unknown. We apply the method to predict the drug response of breast cancer cell lines. GELnet is able to reveal genetic determinants of sensitivity and resistance for several compounds. In particular, for an EGFR/HER2 inhibitor, it finds a possible trans-differentiation resistance mechanism missed by the corresponding pathway agnostic approach.

Published
2016

15. Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions

Author

Pietras, Eric M, Reynaud, Damien, Kang, Yoon-A, Carlin, Daniel, Calero-Nieto, Fernando J, Leavitt, Andrew D, Stuart, Joshua M, Göttgens, Berthold, and Passegué, Emmanuelle

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Stem Cell Research - Nonembryonic - Non-Human, Regenerative Medicine, Stem Cell Research, Hematology, HIV/AIDS, 1.1 Normal biological development and functioning, Underpinning research, Inflammatory and immune system, Blood, Animals, Cell Differentiation, Cell Lineage, Cellular Reprogramming, Gene Expression, Hematopoiesis, Hematopoietic Stem Cells, Lymphoid Progenitor Cells, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Multipotent Stem Cells, Myeloid Progenitor Cells, Regeneration, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Despite great advances in understanding the mechanisms underlying blood production, lineage specification at the level of multipotent progenitors (MPPs) remains poorly understood. Here, we show that MPP2 and MPP3 are distinct myeloid-biased MPP subsets that work together with lymphoid-primed MPP4 cells to control blood production. We find that all MPPs are produced in parallel by hematopoietic stem cells (HSCs), but with different kinetics and at variable levels depending on hematopoietic demands. We also show that the normally rare myeloid-biased MPPs are transiently overproduced by HSCs in regenerating conditions, hence supporting myeloid amplification to rebuild the hematopoietic system. This shift is accompanied by a reduction in self-renewal activity in regenerating HSCs and reprogramming of MPP4 fate toward the myeloid lineage. Our results support a dynamic model of blood development in which HSCs convey lineage specification through independent production of distinct lineage-biased MPP subsets that, in turn, support lineage expansion and differentiation.

Published
2015

18. Discovering causal pathways linking genomic events to transcriptional states using Tied Diffusion Through Interacting Events (TieDIE)

Author

Paull, Evan O, Carlin, Daniel E, Niepel, Mario, Sorger, Peter K, Haussler, David, and Stuart, Joshua M

Subjects
Biochemistry and Cell Biology, Bioinformatics and Computational Biology, Genetics, Biological Sciences, Human Genome, Cancer, Aetiology, 2.1 Biological and endogenous factors, Breast Neoplasms, Cell Line, Tumor, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Genomics, Humans, Neoplasms, Protein Interaction Mapping, Signal Transduction, Software, Transcription Factors, Mathematical Sciences, Information and Computing Sciences, Bioinformatics, Biological sciences, Information and computing sciences, Mathematical sciences
Abstract

MotivationIdentifying the cellular wiring that connects genomic perturbations to transcriptional changes in cancer is essential to gain a mechanistic understanding of disease initiation, progression and ultimately to predict drug response. We have developed a method called Tied Diffusion Through Interacting Events (TieDIE) that uses a network diffusion approach to connect genomic perturbations to gene expression changes characteristic of cancer subtypes. The method computes a subnetwork of protein-protein interactions, predicted transcription factor-to-target connections and curated interactions from literature that connects genomic and transcriptomic perturbations.ResultsApplication of TieDIE to The Cancer Genome Atlas and a breast cancer cell line dataset identified key signaling pathways, with examples impinging on MYC activity. Interlinking genes are predicted to correspond to essential components of cancer signaling and may provide a mechanistic explanation of tumor character and suggest subtype-specific drug targets.AvailabilitySoftware is available from the Stuart lab's wiki: https://sysbiowiki.soe.ucsc.edu/tiedie.Contactjstuart@ucsc.edu.Supplementary informationSupplementary data are available at Bioinformatics online.

Published
2013

20. Supplement to: Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas.

Author

Brat, Daniel J, Verhaak, Roel GW, Salama, Sofie R., Cooper, Lee, Aldape, Kenneth D, Yung, Alfred W.K, Akbani, Rehan, Barnholtz-Sloan, Jill S., Berger, Mitchel S., Brennan, Cameron, Bristow, Christopher A., Cherniack, Andrew D., Ciriello, Giovanni, Colen, Rivka, Colman, Howard, Flanders, Adam E., Giannini, Caterina, Grifford, Mia, Huse, Jason T., Iavarone, Antonio, Jain, Rajan, Joseph, Isaac, Kim, Jaegil, Kasaian, Katayoon, Laird, Peter W., Mikkelsen, Tom, Miller, Ryan C., Morozova, Olena, Murray, Bradley A., Noushmehr, Houtan, OʼNeill, Brian Patrick, Pachter, Lior, Parsons, Donald W., Poisson, Laila M., Rheinbay, Esther, Robertson, Gordon A., Sougnez, Carrie, Sulman, Erik P., Vandenberg, Scott R., Van Meir, Erwin G., Vitucci, Mark, Deimling, Andreas von, Yoshihara, Kosuke, Zhang, Hailei, Zheng, Siyuan, Crain, Daniel, Lau, Kevin, Mallery, David, Morris, Scott, Paulauskis, Joseph, Penny, Robert, Shelton, Troy, Sherman, Mark, Yena, Peggy, Black, Aaron, Bowen, Jay, Dicostanzo, Katie, Gastier-Foster, Julie, Leraas, Kristen M., Lichtenberg, Tara M., Pierson, Christopher R., Ramirez, Nilsa C., Taylor, Cynthia, Weaver, Stephanie, Wise, Lisa, Zmuda, Erik, Davidsen, Tanja, Demchok, John A., Eley, Greg, Ferguson, Martin L., Hutter, Carolyn M., Mills Shaw, Kenna R., Ozenberger, Bradley A., Sheth, Margi, Sofia, Heidi J., Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean Claude, Ayala, Brenda, Baboud, Julien, Chudamani, Sudha, Jensen, Mark A., Liu, Jia, Pihl, Todd, Raman, Rohini, Wan, Yunhu, Wu, Ye, Ally, Adrian, Auman, Todd J., Balasundaram, Miruna, Balu, Saianand, Baylin, Stephen B., Beroukhim, Rameen, Bootwalla, Moiz S., Bowlby, Reanne, Brooks, Denise, Butterfield, Yaron, Carlsen, Rebecca, Carter, Scott, Chin, Lynda, Chu, Andy, Chuah, Eric, Cibulskis, Kristian, Clarke, Amanda, Coetzee, Simon G., Dhalla, Noreen, Fennell, Tim, Fisher, Sheila, Gabriel, Stacey, Getz, Gad, Gibbs, Richard, Grimsby, Jonna L., Guin, Ranabir, Hadjipanayis, Angela, Hayes, Neil D., Hinoue, Toshinori, Hoadley, Katherine, Holt, Robert A., Hoyle, Alan P., Huang, Franklin, Jefferys, Stuart R., Jones, Steven, Jones, Corbin D., Kucherlapati, Raju, Lai, Phillip H., Lander, Eric, Lee, Semin, Lichtenstein, Lee, Ma, Yussanne, Maglinte, Dennis T., Mahadeshwar, Harshad S., Marra, Marco A., Mayo, Michael, Meng, Shaowu, Meyerson, Matthew L., Mieczkowski, Piotr A., Moore, Richard A., Mose, Lisle E., Mungall, Andrew J., Pantazi, Angeliki, Parfenov, Michael, Park, Peter J., Parker, Joel S., Perou, Charles M., Protopopov, Alexei, Ren, Xiaojia, Roach, Jeffrey, Rosenberg, Mara, Sabedot, Thaís S., Sadeghi, Sara, Schein, Jacqueline, Schumacher, Steven E., Seidman, Jonathan G., Seth, Sahil, Shen, Hui, Simons, Janae V., Sipahimalani, Payal, Soloway, Matthew G., Song, Xingzhi, Stewart, Chip, Sun, Huandong, Tabak, Barbara, Tam, Angela, Tan, Donghui, Tang, Jiabin, Thiessen, Nina, Triche, Timothy, Jr., Van Den Berg, David J., Veluvolu, Umadevi, Waring, Scot, Weisenberger, Daniel J., Wilkerson, Matthew D., Wong, Tina, Wu, Junyuan, Xi, Liu, Xu, Andrew W., Yang, Lixing, Zack, Travis I., Zhang, Jianhua, Aksoy, Arman B., Arachchi, Harindra, Benz, Chris, Bernard, Brady, Carlin, Daniel, Cho, Juok, DiCara, Daniel, Frazer, Scott, Fuller, Gregory N., Gao, JianJiong, Gehlenborg, Nils, Haussler, David, Heiman, David I., Iype, Lisa, Jacobsen, Anders, Ju, Zhenlin, Katzman, Sol, Kim, Hoon, Knijnenburg, Theo, Kreisberg, Richard Bailey, Lawrence, Michael S., Lee, William, Leinonen, Kalle, Lin, Pei, Ling, Shiyun, Liu, Wenbin, Liu, Yingchun, Liu, Yuexin, Lu, Yiling, Mills, Gordon, Ng, Sam, Noble, Michael S., Paull, Evan, Radenbaugh, Amie J., Rao, Arvind, Reynolds, Sheila, Saksena, Gordon, Sanborn, Zack, Sander, Chris, Schultz, Nikolaus, Senbabaoglu, Yasin, Shen, Ronglai, Shmulevich, Ilya, Sinha, Rileen, Stuart, Josh, Sumer, Onur S., Sun, Yichao, Tasman, Natalie, Taylor, Barry S., Voet, Doug, Weinhold, Nils, Weinstein, John N., Yang, Da, Zhang, Wei, Zou, Lihua, Abel, Ty, Brat, Daniel J., Cohen, Mark L., Eschbacher, Jenny, Hattab, Eyas M., Raghunathan, Aditya, Schniederjan, Matthew J., Aziz, Dina, Barnett, Gene, Barrett, Wendi, Bigner, Darell D., Boice, Lori, Brewer, Cathy, Calatozzolo, Chiara, Carlotti, Carlos Gilberto, Jr, Chan, Timothy A., Cuppini, Lucia, Curley, Erin, Cuzzubbo, Stefania, Devine, Karen, DiMeco, Francesco, Duell, Rebecca, Elder, Bradley J, Fehrenbach, Ashley, Finocchiaro, Gaetano, Friedman, William, Fulop, Jordonna, Gardner, Johanna, Hermes, Beth, Kendler, Ady, Lehman, Norman L., Lipp, Eric, Liu, Ouida, Mandt, Randy, McGraw, Mary, McLendon, Roger, McPherson, Christopher, Neder, Luciano, Nguyen, Phuong, Noss, Ardene, Nunziata, Raffaele, Ostrom, Quinn T., Palmer, Cheryl, Perin, Alessandro, Pollo, Bianca, Potapov, Alexander, Potapova, Olga, Rathmell, Kimryn W., Rotin, Daniil, Scarpace, Lisa, Schilero, Cathy, Senecal, Kelly, Shimmel, Kristen, Shurkhay, Vsevolod, Sifri, Suzanne, Singh, Rosy, Sloan, Andrew E., Smolenski, Kathy, Staugaitis, Susan M., Steele, Ruth, Thorne, Leigh, Tirapelli, Daniela P.C., Vallurupalli, Mahitha, Wang, Yun, Warnick, Ronald, Williams, Felicia, Wolinsky, Yingli, Zhang, Jianan, Bell, Sue, Campos, Benito, Herold-Mende, Christel, Jungk, Christine, and Unterberg, Andreas

Published
2015

23. COMPUTATIONAL EVALUATION AND DERIVATION OF BIOLOGICAL NETWORKS IN CANCER AND STEM CELLS

Author

Carlin, Daniel Edward

Subjects
Bioinformatics, cancer, network biology, stem cells
Abstract

Biological network models have become standard tools for genome-wide analysis of both cancer disease processes and healthy differentiation from stem cells. In this thesis, I ad- dress a method for evaluating network models in terms of their ability to predict held out expression data given information about other genes in the same network. I apply this test to several extensions of our pathway database to demonstrate the transcrip- tional modeling utility of reverse phase protein array data, natural language processed literature, and transcription factor target predictions in stem cells and differentiated tissue. I then explore the addition of one new type of network data; co-localization in DNA domains. However, preexisting functional data is not the only source of networks. In the final part of the thesis, I elucidate a method to integrate prior biological knowl- edge with time series observations to infer causal relationships between phosphorylation events on proteins.

Published
2014

24. Comprehensive molecular characterization of urothelial bladder carcinoma

Author

Weinstein, John N., Akbani, Rehan, Broom, Bradley M., Wang, Wenyi, Verhaak, Roeland G. W., McConkey, David, Lerner, Seth, Morgan, Margaret, Creighton, Chad J., Smith, Carolyn, Kwiatkowski, David J., Cherniack, Andrew D., Kim, Jaegil, Pedamallu, Chandra Sekhar, Noble, Michael S., Al-Ahmadie, Hikmat A., Reuter, Victor E., Rosenberg, Jonathan E., Bajorin, Dean F., Bochner, Bernard H., Solit, David B., Koppie, Theresa, Robinson, Brian, Gordenin, Dmitry A., Fargo, David, Klimczak, Leszek J., Roberts, Steven A., Au, Jessie, Laird, Peter W., Hinoue, Toshinori, Schultz, Nikolaus, Ramirez, Ricardo, Hansel, Donna, Hoadley, Katherine A., Kim, William Y., Damrauer, Jeffrey S., Baylin, Stephen B., Mungall, Andrew J., Robertson, Gordon A., Chu., Andy, Sougnez, Carrie, Cibulskis, Kristian, Lichtenstein, Lee, Sivachenko, Andrey, Stewart, Chip, Lawrence, Michael S., Getz, Gad, Lander, Eric, Gabriel., Stacey B., Donehower, Lawrence, Carter, Scott L., Saksena, Gordon, Schumacher, Steven E., Freeman, Samuel S., Jung, Joonil, Bhatt, Ami S., Pugh, Trevor, Beroukhim, Rameen, Gabriel, Stacey B., Meyerson, Matthew, Chu, Andy, Ally, Adrian, Balasundaram, Miruna, Butterfield, Yaron S. N., Dhalla, Noreen, Hirst, Carrie, Holt, Robert A., Jones, Steven J. M., Lee, Darlene, Li, Haiyan I., Marra, Marco A., Mayo, Michael, Moore, Richard A., Schein, Jacqueline E., Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Wong, Tina, Wye, Natasja, Bowlby, Reanne, Chuah, Eric, Guin, Ranabir, Shen, Hui, Bootwalla, Moiz S., Jr, Timothy Triche, Lai, Phillip H., Van Den Berg, David J., Weisenberger, Daniel J., Balu, Saianand, Bodenheimer, Tom, Damrauer Alan P. Hoyle, Jeffrey S., Jefferys, Stuart R., Meng, Shaowu, Mose, Lisle E., Simons, Janae V., Soloway, Mathew G., Wu, Junyuan, Parker, Joel S., Hayes, Neil D., Roach, Jeffrey, Buda, Elizabeth, Jones, Corbin D., Mieczkowski, Piotr A., Tan, Donghui, Veluvolu, Umadevi, Waring, Scot, Auman, Todd J., Perou, Charles M., Wilkerson, Matthew D., Santoso, Netty, Parfenov, Michael, Ren, Xiaojia, Pantazi, Angeliki, Hadjipanayis, Angela, Seidman, Jonathan, Kucherlapati, Raju, Lee, Semin, Yang, Lixing, Park, Peter J., Xu, Andrew Wei, Protopopov, Alexei, Zhang, Jianhua, Bristow, Christopher, Mahadeshwar, Harshad S., Seth, Sahil, Song, Xingzhi, Tang, Jiabin, Zeng, Dong, Chin, Lynda, Guo, Charles, Casasent, Tod D., Liu, Wenbin, Ju, Zhenlin, Motter, Thomas, Peng, Bo, Ryan, Michael, Su, Xiaoping, Yang, Ji-Yeon, Lorenzi, Philip L., Yao, Hui, Zhang, Nianxiang, Zhang, Jiexin, Mills, Gordon B., Cho, Juok, DiCara, Daniel, Frazer, Scott, Gehlenborg, Nils, Heiman, David I., Lin, Pei, Liu, Yingchun, Stojanov, Petar, Voet, Doug, Zhang, Hailei, Zou, Lihua, Bernard, Brady, Kreisberg, Dick, Reynolds, Sheila, Rovira, Hector, Shmulevich, Ilya, Gao, Jianjiong, Jacobsen, Anders, Aksoy, Arman B., Antipin, Yevgeniy, Ciriello, Giovanni, Dresdner, Gideon, Gross, Benjamin, Lee, William, Reva, Boris, Shen, Ronglai, Sinha, Rileen, Sumer, Onur S., Weinhold, Nils, Ladanyi, Marc, Sander, Chris, Benz, Christopher, Carlin, Daniel, Haussler, David, Ng, Sam, Paull, Evan O., Stuart, Joshua, Zhu, Jing, Liu, Yuexin, Zhang, Wei, Taylor, Barry S., Lichtenberg, Tara M., Zmuda, Erik, Barr, Thomas, Black, Aaron D., George, Myra, Hanf, Benjamin, Helsel, Carmen, McAllister, Cynthia, Ramirez, Nilsa C., Tabler, Teresa R., Weaver, Stephanie, Wise, Lisa, Bowen, Jay, Gastier-Foster, Julie M., Jian, Weiguo, Tello, Sebrina, Ittman, Michael, Castro, Patricia, McClenden, Whitney D., Gibbs, Richard, Saller, Charles, Tarvin, Katherine, DiPiero, Jennifer M., Owens, Jennifer, Bollag, Roni, Li, Qiang, Weinberger, Paul, Czerwinski, Christine, Huelsenbeck-Dill, Lori, Iacocca, Mary, Petrelli, Nicholas, Rabeno, Brenda, Swanson, Pat, Shelton, Troy, Curley, Erin, Gardner, Johanna, Mallery, David, Penny, Robert, Van Bang, Nguyen, Thi Hanh, Phan, Kohl, Bernard, Van Le, Xuan, Duc Phu, Bui, Thorp, Richard, Tien, Nguyen Viet, Vinh, Le Quang, Sandusky, George, Burks, Eric, Christ, Kimberly, Gee, Jason, Holway, Antonia, Moinzadeh, Alireza, Sorcini, Andrea, Sullivan, Travis, Garcia-Grossman, Ilana R., Regazzi, Ashley M., Boice, Lori, Rathmell, Wendy Kimryn, Thorne, Leigh, Bastacky, Sheldon, Davies, Benjamin, Dhir, Rajiv, Gingrich, Jeffrey, Hrebinko, Ronald, Maranchie, Jodi, Nelson, Joel, Parwani, Anil, Bshara, Wiam, Gaudioso, Carmelo, Morrison, Carl, Alexopoulou, Vina, Bartlett, John, Engel, Jay, Kodeeswaran, Sugy, Antic, Tatjana, O’Donnell, Peter H., Smith, Norm D., Steinberg, Gary D., Egea, Sophie, Gomez-Fernandez, Carmen, Herbert, Lynn, Jorda, Merce, Soloway, Mark, Beaver, Allison, Carter, Suzie, Kapur, Payal, Lewis, Cheryl, Lotan, Yair, Bondaruk, Jolanta, Czerniak, Bogdan, Skinner, Eila, Aldape, Kenneth, Jensen, Mark A., Kahn, Ari B., Pihl, Todd D., Pot, David A., Srinivasan, Deepak, Wan, Yunhu, Ferguson, Martin L., Zenklusen, Jean Claude, Davidsen, Tanja, Demchok, John A., Mills Shaw, Kenna R., Sheth, Margi, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Hutter, Carolyn, Ozenberger, Bradley A., Sofia, Heidi J., and Eley, Greg

Published
2014
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26. Comprehensive molecular characterization of clear cell renal cell carcinoma

Author

Creighton, Chad J., Morgan, Margaret, Gunaratne, Preethi H., Wheeler, David A., Gibbs, Richard A., Robertson, Gordon A., Chu, Andy, Beroukhim, Rameen, Cibulskis, Kristian, Signoretti, Sabina, Hsin-Ta Wu, Fabio Vandin, Raphael, Benjamin J., Verhaak, Roel G. W., Tamboli, Pheroze, Torres-Garcia, Wandaliz, Akbani, Rehan, Weinstein, John N., Reuter, Victor, Hsieh, James J., Brannon, Rose A., Ari Hakimi, A., Jacobsen, Anders, Ciriello, Giovanni, Reva, Boris, Ricketts, Christopher J., Linehan, Marston W., Stuart, Joshua M., Rathmell, Kimryn W., Shen, Hui, Laird, Peter W., Muzny, Donna, Davis, Caleb, Xi, Liu, Chang, Kyle, Kakkar, Nipun, Treviño, Lisa R., Benton, Susan, Reid, Jeffrey G., Morton, Donna, Doddapaneni, Harsha, Han, Yi, Lewis, Lora, Dinh, Huyen, Kovar, Christie, Zhu, Yiming, Santibanez, Jireh, Wang, Min, Hale, Walker, Kalra, Divya, Getz, Gad, Lawrence, Michael S., Sougnez, Carrie, Carter, Scott L., Sivachenko, Andrey, Lichtenstein, Lee, Stewart, Chip, Voet, Doug, Fisher, Sheila, Gabriel, Stacey B., Lander, Eric, Schumacher, Steve E., Tabak, Barbara, Saksena, Gordon, Onofrio, Robert C., Cherniack, Andrew D., Gentry, Jeff, Ardlie, Kristin, Meyerson, Matthew, Chun, Hye-Jung E., Mungall, Andrew J., Sipahimalani, Payal, Stoll, Dominik, Ally, Adrian, Balasundaram, Miruna, Butterfield, Yaron S. N., Carlsen, Rebecca, Carter, Candace, Chuah, Eric, Coope, Robin J. N., Dhalla, Noreen, Gorski, Sharon, Guin, Ranabir, Hirst, Carrie, Hirst, Martin, Holt, Robert A., Lebovitz, Chandra, Lee, Darlene, Li, Haiyan I., Mayo, Michael, Moore, Richard A., Pleasance, Erin, Plettner, Patrick, Schein, Jacqueline E., Shafiei, Arash, Slobodan, Jared R., Tam, Angela, Thiessen, Nina, Varhol, Richard J., Wye, Natasja, Zhao, Yongjun, Birol, Inanc, Jones, Steven J. M., Marra, Marco A., Auman, Todd J., Tan, Donghui, Jones, Corbin D., Hoadley, Katherine A., Mieczkowski, Piotr A., Mose, Lisle E., Jefferys, Stuart R., Topal, Michael D., Liquori, Christina, Turman, Yidi J., Shi, Yan, Waring, Scot, Buda, Elizabeth, Walsh, Jesse, Wu, Junyuan, Bodenheimer, Tom, Hoyle, Alan P., Simons, Janae V., Soloway, Mathew G., Balu, Saianand, Parker, Joel S., Hayes, Neil D., Perou, Charles M., Kucherlapati, Raju, Park, Peter, Triche, Timothy, Jr, Weisenberger, Daniel J., Lai, Phillip H., Bootwalla, Moiz S., Maglinte, Dennis T., Mahurkar, Swapna, Berman, Benjamin P., Van Den Berg, David J., Cope, Leslie, Baylin, Stephen B., Noble, Michael S., DiCara, Daniel, Zhang, Hailei, Cho, Juok, Heiman, David I., Gehlenborg, Nils, Mallard, William, Lin, Pei, Frazer, Scott, Stojanov, Petar, Liu, Yingchun, Zhou, Lihua, Kim, Jaegil, Chin, Lynda, Vandin, Fabio, Wu, Hsin-Ta, Benz, Christopher, Yau, Christina, Reynolds, Sheila M., Shmulevich, Ilya, Verhaak, Roel G.W., Vegesna, Rahul, Kim, Hoon, Zhang, Wei, Cogdell, David, Jonasch, Eric, Ding, Zhiyong, Lu, Yiling, Zhang, Nianxiang, Unruh, Anna K., Casasent, Tod D., Wakefield, Chris, Tsavachidou, Dimitra, Mills, Gordon B., Schultz, Nikolaus, Antipin, Yevgeniy, Gao, Jianjiong, Cerami, Ethan, Gross, Benjamin, Aksoy, Arman B., Sinha, Rileen, Weinhold, Nils, Sumer, Onur S., Taylor, Barry S., Shen, Ronglai, Ostrovnaya, Irina, Berger, Michael F., Ladanyi, Marc, Sander, Chris, Fei, Suzanne S., Stout, Andrew, Spellman, Paul T., Rubin, Daniel L., Liu, Tiffany T., Ng, Sam, Paull, Evan O., Carlin, Daniel, Goldstein, Theodore, Waltman, Peter, Ellrott, Kyle, Zhu, Jing, Haussler, David, Xiao, Weimin, Shelton, Candace, Gardner, Johanna, Penny, Robert, Sherman, Mark, Mallery, David, Morris, Scott, Paulauskis, Joseph, Burnett, Ken, Shelton, Troy, Kaelin, William G., Choueiri, Toni, Atkins, Michael B., Curley, Erin, Tickoo, Satish, Thorne, Leigh, Boice, Lori, Huang, Mei, Fisher, Jennifer C., Vocke, Cathy D., Peterson, James, Worrell, Robert, Merino, Maria J., Schmidt, Laura S., Czerniak, Bogdan A., Aldape, Kenneth D., Wood, Christopher G., Boyd, Jeff, Weaver, JoEllen, Iacocca, Mary V., Petrelli, Nicholas, Witkin, Gary, Brown, Jennifer, Czerwinski, Christine, Huelsenbeck-Dill, Lori, Rabeno, Brenda, Myers, Jerome, Morrison, Carl, Bergsten, Julie, Eckman, John, Harr, Jodi, Smith, Christine, Tucker, Kelinda, Zach, Leigh Anne, Bshara, Wiam, Gaudioso, Carmelo, Dhir, Rajiv, Maranchie, Jodi, Nelson, Joel, Parwani, Anil, Potapova, Olga, Fedosenko, Konstantin, Cheville, John C., Thompson, Houston R., Mosquera, Juan M., Rubin, Mark A., Blute, Michael L., Pihl, Todd, Jensen, Mark, Sfeir, Robert, Kahn, Ari, Chu, Anna, Kothiyal, Prachi, Snyder, Eric, Pontius, Joan, Ayala, Brenda, Backus, Mark, Walton, Jessica, Baboud, Julien, Berton, Dominique, Nicholls, Matthew, Srinivasan, Deepak, Raman, Rohini, Girshik, Stanley, Kigonya, Peter, Alonso, Shelley, Sanbhadti, Rashmi, Barletta, Sean, Pot, David, Sheth, Margi, Demchok, John A., Davidsen, Tanja, Wang, Zhining, Yang, Liming, Tarnuzzer, Roy W., Zhang, Jiashan, Eley, Greg, Ferguson, Martin L., Mills Shaw, Kenna R., Guyer, Mark S., Ozenberger, Bradley A., and Sofia, Heidi J.

Published
2013
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27. Comprehensive molecular portraits of human breast tumours

Author

Koboldt, Daniel C., Fulton, Robert S., McLellan, Michael D., Schmidt, Heather, Kalicki-Veizer, Joelle, McMichael, Joshua F., Fulton, Lucinda L., Dooling, David J., Ding, Li, Mardis, Elaine R., Wilson, Richard K., Ally, Adrian, Balasundaram, Miruna, Butterfield, Yaron S. N., Carlsen, Rebecca, Carter, Candace, Chu, Andy, Chuah, Eric, Chun, Hye-Jung E., Coope, Robin J. N., Dhalla, Noreen, Guin, Ranabir, Hirst, Carrie, Hirst, Martin, Holt, Robert A., Lee, Darlene, Li, Haiyan I., Mayo, Michael, Moore, Richard A., Mungall, Andrew J., Pleasance, Erin, Gordon Robertson, A., Schein, Jacqueline E., Shafiei, Arash, Sipahimalani, Payal, Slobodan, Jared R., Stoll, Dominik, Tam, Angela, Thiessen, Nina, Varhol, Richard J., Wye, Natasja, Zeng, Thomas, Zhao, Yongjun, Birol, Inanc, Jones, Steven J. M., Marra, Marco A., Cherniack, Andrew D., Saksena, Gordon, Onofrio, Robert C., Pho, Nam H., Carter, Scott L., Schumacher, Steven E., Tabak, Barbara, Hernandez, Bryan, Gentry, Jeff, Nguyen, Huy, Crenshaw, Andrew, Ardlie, Kristin, Beroukhim, Rameen, Winckler, Wendy, Getz, Gad, Gabriel, Stacey B., Meyerson, Matthew, Chin, Lynda, Park, Peter J., Kucherlapati, Raju, Hoadley, Katherine A., Todd Auman, J., Fan, Cheng, Turman, Yidi J., Shi, Yan, Li, Ling, Topal, Michael D., He, Xiaping, Chao, Hann-Hsiang, Prat, Aleix, Silva, Grace O., Iglesia, Michael D., Zhao, Wei, Usary, Jerry, Berg, Jonathan S., Adams, Michael, Booker, Jessica, Wu, Junyuan, Gulabani, Anisha, Bodenheimer, Tom, Hoyle, Alan P., Simons, Janae V., Soloway, Matthew G., Mose, Lisle E., Jefferys, Stuart R., Balu, Saianand, Parker, Joel S., Neil Hayes, D., Perou, Charles M., Malik, Simeen, Mahurkar, Swapna, Shen, Hui, Weisenberger, Daniel J., Triche, Timothy, Jr, Lai, Phillip H., Bootwalla, Moiz S., Maglinte, Dennis T., Berman, Benjamin P., Van Den Berg, David J., Baylin, Stephen B., Laird, Peter W., Creighton, Chad J., Donehower, Lawrence A., Noble, Michael, Voet, Doug, Gehlenborg, Nils, DiCara, Daniel, Zhang, Juinhua, Zhang, Hailei, Wu, Chang-Jiun, Liu, Spring Yingchun, Lawrence, Michael S., Zou, Lihua, Sivachenko, Andrey, Lin, Pei, Stojanov, Petar, Jing, Rui, Cho, Juok, Sinha, Raktim, Park, Richard W., Nazaire, Marc-Danie, Robinson, Jim, Thorvaldsdottir, Helga, Mesirov, Jill, Reynolds, Sheila, Kreisberg, Richard B., Bernard, Brady, Bressler, Ryan, Erkkila, Timo, Lin, Jake, Thorsson, Vesteinn, Zhang, Wei, Shmulevich, Ilya, Ciriello, Giovanni, Weinhold, Nils, Schultz, Nikolaus, Gao, Jianjiong, Cerami, Ethan, Gross, Benjamin, Jacobsen, Anders, Sinha, Rileen, Arman Aksoy, B., Antipin, Yevgeniy, Reva, Boris, Shen, Ronglai, Taylor, Barry S., Ladanyi, Marc, Sander, Chris, Anur, Pavana, Spellman, Paul T., Lu, Yiling, Liu, Wenbin, Verhaak, Roel R. G., Mills, Gordon B., Akbani, Rehan, Zhang, Nianxiang, Broom, Bradley M., Casasent, Tod D., Wakefield, Chris, Unruh, Anna K., Baggerly, Keith, Coombes, Kevin, Weinstein, John N., Haussler, David, Benz, Christopher C., Stuart, Joshua M., Benz, Stephen C., Zhu, Jingchun, Szeto, Christopher C., Scott, Gary K., Yau, Christina, Paull, Evan O., Carlin, Daniel, Wong, Christopher, Sokolov, Artem, Thusberg, Janita, Mooney, Sean, Ng, Sam, Goldstein, Theodore C., Ellrott, Kyle, Grifford, Mia, Wilks, Christopher, Ma, Singer, Craft, Brian, Yan, Chunhua, Hu, Ying, Meerzaman, Daoud, Gastier-Foster, Julie M., Bowen, Jay, Ramirez, Nilsa C., Black, Aaron D., Pyatt, Robert E., White, Peter, Zmuda, Erik J., Frick, Jessica, Lichtenberg, Tara M., Brookens, Robin, George, Myra M., Gerken, Mark A., Harper, Hollie A., Leraas, Kristen M., Wise, Lisa J., Tabler, Teresa R., McAllister, Cynthia, Barr, Thomas, Hart-Kothari, Melissa, Tarvin, Katie, Saller, Charles, Sandusky, George, Mitchell, Colleen, Iacocca, Mary V., Brown, Jennifer, Rabeno, Brenda, Czerwinski, Christine, Petrelli, Nicholas, Dolzhansky, Oleg, Abramov, Mikhail, Voronina, Olga, Potapova, Olga, Marks, Jeffrey R., Suchorska, Wiktoria M., Murawa, Dawid, Kycler, Witold, Ibbs, Matthew, Korski, Konstanty, Spychała, Arkadiusz, Murawa, Paweł, Brzeziński, Jacek J., Perz, Hanna, Łaźniak, Radosław, Teresiak, Marek, Tatka, Honorata, Leporowska, Ewa, Bogusz-Czerniewicz, Marta, Malicki, Julian, Mackiewicz, Andrzej, Wiznerowicz, Maciej, Van Le, Xuan, Kohl, Bernard, Viet Tien, Nguyen, Thorp, Richard, Van Bang, Nguyen, Sussman, Howard, Duc Phu, Bui, Hajek, Richard, Phi Hung, Nguyen, Viet The Phuong, Tran, Quyet Thang, Huynh, Zaki Khan, Khurram, Penny, Robert, Mallery, David, Curley, Erin, Shelton, Candace, Yena, Peggy, Ingle, James N., Couch, Fergus J., Lingle, Wilma L., King, Tari A., Maria Gonzalez-Angulo, Ana, Dyer, Mary D., Liu, Shuying, Meng, Xiaolong, Patangan, Modesto, Waldman, Frederic, Stöppler, Hubert, Kimryn Rathmell, W., Thorne, Leigh, Huang, Mei, Boice, Lori, Hill, Ashley, Morrison, Carl, Gaudioso, Carmelo, Bshara, Wiam, Daily, Kelly, Egea, Sophie C., Pegram, Mark D., Gomez-Fernandez, Carmen, Dhir, Rajiv, Bhargava, Rohit, Brufsky, Adam, Shriver, Craig D., Hooke, Jeffrey A., Leigh Campbell, Jamie, Mural, Richard J., Hu, Hai, Somiari, Stella, Larson, Caroline, Deyarmin, Brenda, Kvecher, Leonid, Kovatich, Albert J., Ellis, Matthew J., Stricker, Thomas, White, Kevin, Olopade, Olufunmilayo, Luo, Chunqing, Chen, Yaqin, Bose, Ron, Chang, Li-Wei, Beck, Andrew H., Pihl, Todd, Jensen, Mark, Sfeir, Robert, Kahn, Ari, Chu, Anna, Kothiyal, Prachi, Wang, Zhining, Snyder, Eric, Pontius, Joan, Ayala, Brenda, Backus, Mark, Walton, Jessica, Baboud, Julien, Berton, Dominique, Nicholls, Matthew, Srinivasan, Deepak, Raman, Rohini, Girshik, Stanley, Kigonya, Peter, Alonso, Shelley, Sanbhadti, Rashmi, Barletta, Sean, Pot, David, Sheth, Margi, Demchok, John A., Mills Shaw, Kenna R., Yang, Liming, Eley, Greg, Ferguson, Martin L., Tarnuzzer, Roy W., Zhang, Jiashan, Dillon, Laura A. L., Buetow, Kenneth, Fielding, Peter, Ozenberger, Bradley A., Guyer, Mark S., Sofia, Heidi J., and Palchik, Jacqueline D.

Published
2012
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28. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Author

Menden, Michael P., Wang, Dennis, Mason, Mike J., Szalai, Bence, Bulusu, Krishna C., Guan, Yuanfang, Yu, Thomas, Kang, Jaewoo, Jeon, Minji, Wolfinger, Russ, Nguyen, Tin, Zaslavskiy, Mikhail, Jang, In Sock, Ghazoui, Zara, Ahsen, Mehmet Eren, Vogel, Robert, Neto, Elias Chaibub, Norman, Thea, Tang, Eric K. Y., Garnett, Mathew J., Di Veroli, Giovanni Y., Fawell, Stephen, Stolovitzky, Gustavo, Guinney, Justin, Dry, Jonathan R., Saez-Rodriguez, Julio, Abante, Jordi, Abecassis, Barbara Schmitz, Aben, Nanne, Aghamirzaie, Delasa, Aittokallio, Tero, Akhtari, Farida S., Al-lazikani, Bissan, Alam, Tanvir, Allam, Amin, Allen, Chad, de Almeida, Mariana Pelicano, Altarawy, Doaa, Alves, Vinicius, Amadoz, Alicia, Anchang, Benedict, Antolin, Albert A., Ash, Jeremy R., Romeo Aznar, Victoria, Ba-alawi, Wail, Bagheri, Moeen, Bajic, Vladimir, Ball, Gordon, Ballester, Pedro J., Baptista, Delora, Bare, Christopher, Bateson, Mathilde, Bender, Andreas, Bertrand, Denis, Wijayawardena, Bhagya, Boroevich, Keith A., Bosdriesz, Evert, Bougouffa, Salim, Bounova, Gergana, Brouwer, Thomas, Bryant, Barbara, Calaza, Manuel, Calderone, Alberto, Calza, Stefano, Capuzzi, Stephen, Carbonell-Caballero, Jose, Carlin, Daniel, Carter, Hannah, Castagnoli, Luisa, Celebi, Remzi, Cesareni, Gianni, Chang, Hyeokyoon, Chen, Guocai, Chen, Haoran, Chen, Huiyuan, Cheng, Lijun, Chernomoretz, Ariel, Chicco, Davide, Cho, Kwang-Hyun, Cho, Sunghwan, Choi, Daeseon, Choi, Jaejoon, Choi, Kwanghun, Choi, Minsoo, De Cock, Martine, Coker, Elizabeth, Cortes-Ciriano, Isidro, Cserzo, Miklos, Cubuk, Cankut, Curtis, Christina, Van Daele, Dries, Dang, Cuong C., Dijkstra, Tjeerd, Dopazo, Joaquin, Draghici, Sorin, Drosou, Anastasios, Dumontier, Michel, Ehrhart, Friederike, Eid, Fatma-Elzahraa, ElHefnawi, Mahmoud, Elmarakeby, Haitham A., van Engelen, Bo, Engin, Hatice Billur, de Esch, Iwan, Evelo, Chris, Falcao, Andre O., Farag, Sherif, Fernandez-Lozano, Carlos, Fisch, Kathleen, Flobak, Asmund, Fornari, Chiara, Foroushani, Amir B. K., Fotso, Donatien Chedom, Fourches, Denis, Friend, Stephen, Frigessi, Arnoldo, Gao, Feng, Gao, Xiaoting, Gerold, Jeffrey M., Gestraud, Pierre, Ghosh, Samik, Gillberg, Jussi, Godoy-Lorite, Antonia, Godynyuk, Lizzy, Godzik, Adam, Goldenberg, Anna, Gomez-Cabrero, David, Gonen, Mehmet, de Graaf, Chris, Gray, Harry, Grechkin, Maxim, Guimera, Roger, Guney, Emre, Haibe-Kains, Benjamin, Han, Younghyun, Hase, Takeshi, He, Di, He, Liye, Heath, Lenwood S., Hellton, Kristoffer H., Helmer-Citterich, Manuela, Hidalgo, Marta R., Hidru, Daniel, Hill, Steven M., Hochreiter, Sepp, Hong, Seungpyo, Hovig, Eivind, Hsueh, Ya-Chih, Hu, Zhiyuan, Huang, Justin K., Huang, R. Stephanie, Hunyady, Laszlo, Hwang, Jinseub, Hwang, Tae Hyun, Hwang, Woochang, Hwang, Yongdeuk, Isayev, Olexandr, Walk, Oliver Bear Don't, Jack, John, Jahandideh, Samad, Ji, Jiadong, Jo, Yousang, Kamola, Piotr J., Kanev, Georgi K., Karacosta, Loukia, Karimi, Mostafa, Kaski, Samuel, Kazanov, Marat, Khamis, Abdullah M., Khan, Suleiman Ali, Kiani, Narsis A., Kim, Allen, Kim, Jinhan, Kim, Juntae, Kim, Kiseong, Kim, Kyung, Kim, Sunkyu, Kim, Yongsoo, Kim, Yunseong, Kirk, Paul D. W., Kitano, Hiroaki, Klambauer, Gunter, Knowles, David, Ko, Melissa, Kohn-Luque, Alvaro, Kooistra, Albert J., Kuenemann, Melaine A., Kuiper, Martin, Kurz, Christoph, Kwon, Mijin, van Laarhoven, Twan, Laegreid, Astrid, Lederer, Simone, Lee, Heewon, Lee, Jeon, Lee, Yun Woo, Leppaho, Eemeli, Lewis, Richard, Li, Jing, Li, Lang, Liley, James, Lim, Weng Khong, Lin, Chieh, Liu, Yiyi, Lopez, Yosvany, Low, Joshua, Lysenko, Artem, Machado, Daniel, Madhukar, Neel, De Maeyer, Dries, Malpartida, Ana Belen, Mamitsuka, Hiroshi, Marabita, Francesco, Marchal, Kathleen, Marttinen, Pekka, Mason, Daniel, Mazaheri, Alireza, Mehmood, Arfa, Mehreen, Ali, Michaut, Magali, Miller, Ryan A., Mitsopoulos, Costas, Modos, Dezso, Van Moerbeke, Marijke, Moo, Keagan, Motsinger-Reif, Alison, Movva, Rajiv, Muraru, Sebastian, Muratov, Eugene, Mushthofa, Mushthofa, Nagarajan, Niranjan, Nakken, Sigve, Nath, Aritro, Neuvial, Pierre, Newton, Richard, Ning, Zheng, De Niz, Carlos, Oliva, Baldo, Olsen, Catharina, Palmeri, Antonio, Panesar, Bhawan, Papadopoulos, Stavros, Park, Jaesub, Park, Seonyeong, Park, Sungjoon, Pawitan, Yudi, Peluso, Daniele, Pendyala, Sriram, Peng, Jian, Perfetto, Livia, Pirro, Stefano, Plevritis, Sylvia, Politi, Regina, Poon, Hoifung, Porta, Eduard, Prellner, Isak, Preuer, Kristina, Angel Pujana, Miguel, Ramnarine, Ricardo, Reid, John E., Reyal, Fabien, Richardson, Sylvia, Ricketts, Camir, Rieswijk, Linda, Rocha, Miguel, Rodriguez-Gonzalvez, Carmen, Roell, Kyle, Rotroff, Daniel, de Ruiter, Julian R., Rukawa, Ploy, Sadacca, Benjamin, Safikhani, Zhaleh, Safitri, Fita, Sales-Pardo, Marta, Sauer, Sebastian, Schlichting, Moritz, Seoane, Jose A., Serra, Jordi, Shang, Ming-Mei, Sharma, Alok, Sharma, Hari, Shen, Yang, Shiga, Motoki, Shin, Moonshik, Shkedy, Ziv, Shopsowitz, Kevin, Sinai, Sam, Skola, Dylan, Smirnov, Petr, Soerensen, Izel Fourie, Soerensen, Peter, Song, Je-Hoon, Song, Sang Ok, Soufan, Othman, Spitzmueller, Andreas, Steipe, Boris, Suphavilai, Chayaporn, Tamayo, Sergio Pulido, Tamborero, David, Tang, Jing, Tanoli, Zia-ur-Rehman, Tarres-Deulofeu, Marc, Tegner, Jesper, Thommesen, Liv, Tonekaboni, Seyed Ali Madani, Tran, Hong T., De Troyer, Ewoud, Truong, Amy, Tsunoda, Tatsuhiko, Turu, Gabor, Tzeng, Guang-Yo, Verbeke, Lieven, Videla, Santiago, Vis, Daniel, Voronkov, Andrey, Votis, Konstantinos, Wang, Ashley, Wang, Hong-Qiang Horace, Wang, Po-Wei, Wang, Sheng, Wang, Wei, Wang, Xiaochen, Wang, Xin, Wennerberg, Krister, Wernisch, Lorenz, Wessels, Lodewyk, van Westen, Gerard J. P., Westerman, Bart A., White, Simon Richard, Willighagen, Egon, Wurdinger, Tom, Xie, Lei, Xie, Shuilian, Xu, Hua, Yadav, Bhagwan, Yau, Christopher, Yeerna, Huwate, Yin, Jia Wei, Yu, Michael, Yu, MinHwan, Yun, So Jeong, Zakharov, Alexey, Zamichos, Alexandros, Zanin, Massimiliano, Zeng, Li, Zenil, Hector, Zhang, Frederick, Zhang, Pengyue, Zhang, Wei, Zhao, Hongyu, Zhao, Lan, Zheng, Wenjin, Zoufir, Azedine, Zucknick, Manuela, and Computer Science

Subjects
health care economics and organizations
Abstract

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells. AstraZeneca European Union Horizon 2020 research [668858 PrECISE] Joint Research Center for Computational Biomedicine (Bayer AG) National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences Wellcome Trust [102696, 206194] We thank the Genomics of Drug Sensitivity in Cancer and COSMIC teams at the Wellcome Trust Sanger Institute for help with the preparation of the molecular data, Denes Turei for help with Omnipath, and Katjusa Koler for help with matching drug names across combination screens. We thank AstraZeneca for funding and provision of data to the DREAM Consortium to run the challenge, and funding from the European Union Horizon 2020 research (under grant agreement No 668858 PrECISE to J.S.R.), the Joint Research Center for Computational Biomedicine (which is partially funded by Bayer AG) to J.S.R., National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences. M.G lab is supported by Wellcome Trust (102696 and 206194).

Published
2019

29. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Author

Gönen, Mehmet (ORCID 0000-0002-2483-075X & YÖK ID 237468), Menden, Michael P.; Wang, Dennis; Mason, Mike J.; Szalai, Bence; Bulusu, Krishna C.; Guan, Yuanfang; Yu, Thomas; Kang, Jaewoo; Jeon, Minji; Wolfinger, Russ; Nguyen, Tin; Zaslavskiy, Mikhail; Jang, In Sock; Ghazoui, Zara; Ahsen, Mehmet Eren; Vogel, Robert; Neto, Elias Chaibub; Norman, Thea; Tang, Eric K. Y.; Garnett, Mathew J.; Di Veroli, Giovanni Y.; Fawell, Stephen; Stolovitzky, Gustavo; Guinney, Justin; Dry, Jonathan R.; Saez-Rodriguez, Julio; Abante, Jordi; Abecassis, Barbara Schmitz; Aben, Nanne; Aghamirzaie, Delasa; Aittokallio, Tero; Akhtari, Farida S.; Al-lazikani, Bissan; Alam, Tanvir; Allam, Amin; Allen, Chad; de Almeida, Mariana Pelicano; Altarawy, Doaa; Alves, Vinicius; Amadoz, Alicia; Anchang, Benedict; Antolin, Albert A.; Ash, Jeremy R.; Romeo Aznar, Victoria; Ba-alawi, Wail; Bagheri, Moeen; Bajic, Vladimir; Ball, Gordon; Ballester, Pedro J.; Baptista, Delora; Bare, Christopher; Bateson, Mathilde; Bender, Andreas; Bertrand, Denis; Wijayawardena, Bhagya; Boroevich, Keith A.; Bosdriesz, Evert; Bougouffa, Salim; Bounova, Gergana; Brouwer, Thomas; Bryant, Barbara; Calaza, Manuel; Calderone, Alberto; Calza, Stefano; Capuzzi, Stephen; Carbonell-Caballero, Jose; Carlin, Daniel; Carter, Hannah; Castagnoli, Luisa; Celebi, Remzi; Cesareni, Gianni; Chang, Hyeokyoon; Chen, Guocai; Chen, Haoran; Chen, Huiyuan; Cheng, Lijun; Chernomoretz, Ariel; Chicco, Davide; Cho, Kwang-Hyun; Cho, Sunghwan; Choi, Daeseon; Choi, Jaejoon; Choi, Kwanghun; Choi, Minsoo; De Cock, Martine; Coker, Elizabeth; Cortes-Ciriano, Isidro; Cserzo, Miklos; Cubuk, Cankut; Curtis, Christina; Van Daele, Dries; Dang, Cuong C.; Dijkstra, Tjeerd; Dopazo, Joaquin; Draghici, Sorin; Drosou, Anastasios; Dumontier, Michel; Ehrhart, Friederike; Eid, Fatma-Elzahraa; ElHefnawi, Mahmoud; Elmarakeby, Haitham; van Engelen, Bo; Engin, Hatice Billur; de Esch, Iwan; Evelo, Chris; Falcao, Andre O.; Farag, Sherif; Fernandez-Lozano, Carlos; Fisch, Kathleen; Flobak, Asmund; Fornari, Chiara; Foroushani, Amir B. K.; Fotso, College of Engineering, Department of Industrial Engineering, Gönen, Mehmet (ORCID 0000-0002-2483-075X & YÖK ID 237468), Menden, Michael P.; Wang, Dennis; Mason, Mike J.; Szalai, Bence; Bulusu, Krishna C.; Guan, Yuanfang; Yu, Thomas; Kang, Jaewoo; Jeon, Minji; Wolfinger, Russ; Nguyen, Tin; Zaslavskiy, Mikhail; Jang, In Sock; Ghazoui, Zara; Ahsen, Mehmet Eren; Vogel, Robert; Neto, Elias Chaibub; Norman, Thea; Tang, Eric K. Y.; Garnett, Mathew J.; Di Veroli, Giovanni Y.; Fawell, Stephen; Stolovitzky, Gustavo; Guinney, Justin; Dry, Jonathan R.; Saez-Rodriguez, Julio; Abante, Jordi; Abecassis, Barbara Schmitz; Aben, Nanne; Aghamirzaie, Delasa; Aittokallio, Tero; Akhtari, Farida S.; Al-lazikani, Bissan; Alam, Tanvir; Allam, Amin; Allen, Chad; de Almeida, Mariana Pelicano; Altarawy, Doaa; Alves, Vinicius; Amadoz, Alicia; Anchang, Benedict; Antolin, Albert A.; Ash, Jeremy R.; Romeo Aznar, Victoria; Ba-alawi, Wail; Bagheri, Moeen; Bajic, Vladimir; Ball, Gordon; Ballester, Pedro J.; Baptista, Delora; Bare, Christopher; Bateson, Mathilde; Bender, Andreas; Bertrand, Denis; Wijayawardena, Bhagya; Boroevich, Keith A.; Bosdriesz, Evert; Bougouffa, Salim; Bounova, Gergana; Brouwer, Thomas; Bryant, Barbara; Calaza, Manuel; Calderone, Alberto; Calza, Stefano; Capuzzi, Stephen; Carbonell-Caballero, Jose; Carlin, Daniel; Carter, Hannah; Castagnoli, Luisa; Celebi, Remzi; Cesareni, Gianni; Chang, Hyeokyoon; Chen, Guocai; Chen, Haoran; Chen, Huiyuan; Cheng, Lijun; Chernomoretz, Ariel; Chicco, Davide; Cho, Kwang-Hyun; Cho, Sunghwan; Choi, Daeseon; Choi, Jaejoon; Choi, Kwanghun; Choi, Minsoo; De Cock, Martine; Coker, Elizabeth; Cortes-Ciriano, Isidro; Cserzo, Miklos; Cubuk, Cankut; Curtis, Christina; Van Daele, Dries; Dang, Cuong C.; Dijkstra, Tjeerd; Dopazo, Joaquin; Draghici, Sorin; Drosou, Anastasios; Dumontier, Michel; Ehrhart, Friederike; Eid, Fatma-Elzahraa; ElHefnawi, Mahmoud; Elmarakeby, Haitham; van Engelen, Bo; Engin, Hatice Billur; de Esch, Iwan; Evelo, Chris; Falcao, Andre O.; Farag, Sherif; Fernandez-Lozano, Carlos; Fisch, Kathleen; Flobak, Asmund; Fornari, Chiara; Foroushani, Amir B. K.; Fotso, College of Engineering, and Department of Industrial Engineering

Abstract

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells., AstraZeneca; European Union Horizon 2020 Research; European Union (European Union); Horizon 2020; Joint Research Center for Computational Biomedicine; National Institute for Health Research (NIHR) Sheffield Biomedical Research Center; Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences; Wellcome Trust

Published
2019

30. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Author

Computer Science, Menden, Michael P., Wang, Dennis, Mason, Mike J., Szalai, Bence, Bulusu, Krishna C., Guan, Yuanfang, Yu, Thomas, Kang, Jaewoo, Jeon, Minji, Wolfinger, Russ, Nguyen, Tin, Zaslavskiy, Mikhail, Jang, In Sock, Ghazoui, Zara, Ahsen, Mehmet Eren, Vogel, Robert, Neto, Elias Chaibub, Norman, Thea, Tang, Eric K. Y., Garnett, Mathew J., Di Veroli, Giovanni Y., Fawell, Stephen, Stolovitzky, Gustavo, Guinney, Justin, Dry, Jonathan R., Saez-Rodriguez, Julio, Abante, Jordi, Abecassis, Barbara Schmitz, Aben, Nanne, Aghamirzaie, Delasa, Aittokallio, Tero, Akhtari, Farida S., Al-lazikani, Bissan, Alam, Tanvir, Allam, Amin, Allen, Chad, de Almeida, Mariana Pelicano, Altarawy, Doaa, Alves, Vinicius, Amadoz, Alicia, Anchang, Benedict, Antolin, Albert A., Ash, Jeremy R., Romeo Aznar, Victoria, Ba-alawi, Wail, Bagheri, Moeen, Bajic, Vladimir, Ball, Gordon, Ballester, Pedro J., Baptista, Delora, Bare, Christopher, Bateson, Mathilde, Bender, Andreas, Bertrand, Denis, Wijayawardena, Bhagya, Boroevich, Keith A., Bosdriesz, Evert, Bougouffa, Salim, Bounova, Gergana, Brouwer, Thomas, Bryant, Barbara, Calaza, Manuel, Calderone, Alberto, Calza, Stefano, Capuzzi, Stephen, Carbonell-Caballero, Jose, Carlin, Daniel, Carter, Hannah, Castagnoli, Luisa, Celebi, Remzi, Cesareni, Gianni, Chang, Hyeokyoon, Chen, Guocai, Chen, Haoran, Chen, Huiyuan, Cheng, Lijun, Chernomoretz, Ariel, Chicco, Davide, Cho, Kwang-Hyun, Cho, Sunghwan, Choi, Daeseon, Choi, Jaejoon, Choi, Kwanghun, Choi, Minsoo, De Cock, Martine, Coker, Elizabeth, Cortes-Ciriano, Isidro, Cserzo, Miklos, Cubuk, Cankut, Curtis, Christina, Van Daele, Dries, Dang, Cuong C., Dijkstra, Tjeerd, Dopazo, Joaquin, Draghici, Sorin, Drosou, Anastasios, Dumontier, Michel, Ehrhart, Friederike, Eid, Fatma-Elzahraa, ElHefnawi, Mahmoud, Elmarakeby, Haitham A., van Engelen, Bo, Engin, Hatice Billur, de Esch, Iwan, Evelo, Chris, Falcao, Andre O., Farag, Sherif, Fernandez-Lozano, Carlos, Fisch, Kathleen, Flobak, Asmund, Fornari, Chiara, Foroushani, Amir B. K., Fotso, Donatien Chedom, Fourches, Denis, Friend, Stephen, Frigessi, Arnoldo, Gao, Feng, Gao, Xiaoting, Gerold, Jeffrey M., Gestraud, Pierre, Ghosh, Samik, Gillberg, Jussi, Godoy-Lorite, Antonia, Godynyuk, Lizzy, Godzik, Adam, Goldenberg, Anna, Gomez-Cabrero, David, Gonen, Mehmet, de Graaf, Chris, Gray, Harry, Grechkin, Maxim, Guimera, Roger, Guney, Emre, Haibe-Kains, Benjamin, Han, Younghyun, Hase, Takeshi, He, Di, He, Liye, Heath, Lenwood S., Hellton, Kristoffer H., Helmer-Citterich, Manuela, Hidalgo, Marta R., Hidru, Daniel, Hill, Steven M., Hochreiter, Sepp, Hong, Seungpyo, Hovig, Eivind, Hsueh, Ya-Chih, Hu, Zhiyuan, Huang, Justin K., Huang, R. Stephanie, Hunyady, Laszlo, Hwang, Jinseub, Hwang, Tae Hyun, Hwang, Woochang, Hwang, Yongdeuk, Isayev, Olexandr, Walk, Oliver Bear Don't, Jack, John, Jahandideh, Samad, Ji, Jiadong, Jo, Yousang, Kamola, Piotr J., Kanev, Georgi K., Karacosta, Loukia, Karimi, Mostafa, Kaski, Samuel, Kazanov, Marat, Khamis, Abdullah M., Khan, Suleiman Ali, Kiani, Narsis A., Kim, Allen, Kim, Jinhan, Kim, Juntae, Kim, Kiseong, Kim, Kyung, Kim, Sunkyu, Kim, Yongsoo, Kim, Yunseong, Kirk, Paul D. W., Kitano, Hiroaki, Klambauer, Gunter, Knowles, David, Ko, Melissa, Kohn-Luque, Alvaro, Kooistra, Albert J., Kuenemann, Melaine A., Kuiper, Martin, Kurz, Christoph, Kwon, Mijin, van Laarhoven, Twan, Laegreid, Astrid, Lederer, Simone, Lee, Heewon, Lee, Jeon, Lee, Yun Woo, Leppaho, Eemeli, Lewis, Richard, Li, Jing, Li, Lang, Liley, James, Lim, Weng Khong, Lin, Chieh, Liu, Yiyi, Lopez, Yosvany, Low, Joshua, Lysenko, Artem, Machado, Daniel, Madhukar, Neel, De Maeyer, Dries, Malpartida, Ana Belen, Mamitsuka, Hiroshi, Marabita, Francesco, Marchal, Kathleen, Marttinen, Pekka, Mason, Daniel, Mazaheri, Alireza, Mehmood, Arfa, Mehreen, Ali, Michaut, Magali, Miller, Ryan A., Mitsopoulos, Costas, Modos, Dezso, Van Moerbeke, Marijke, Moo, Keagan, Motsinger-Reif, Alison, Movva, Rajiv, Muraru, Sebastian, Muratov, Eugene, Mushthofa, Mushthofa, Nagarajan, Niranjan, Nakken, Sigve, Nath, Aritro, Neuvial, Pierre, Newton, Richard, Ning, Zheng, De Niz, Carlos, Oliva, Baldo, Olsen, Catharina, Palmeri, Antonio, Panesar, Bhawan, Papadopoulos, Stavros, Park, Jaesub, Park, Seonyeong, Park, Sungjoon, Pawitan, Yudi, Peluso, Daniele, Pendyala, Sriram, Peng, Jian, Perfetto, Livia, Pirro, Stefano, Plevritis, Sylvia, Politi, Regina, Poon, Hoifung, Porta, Eduard, Prellner, Isak, Preuer, Kristina, Angel Pujana, Miguel, Ramnarine, Ricardo, Reid, John E., Reyal, Fabien, Richardson, Sylvia, Ricketts, Camir, Rieswijk, Linda, Rocha, Miguel, Rodriguez-Gonzalvez, Carmen, Roell, Kyle, Rotroff, Daniel, de Ruiter, Julian R., Rukawa, Ploy, Sadacca, Benjamin, Safikhani, Zhaleh, Safitri, Fita, Sales-Pardo, Marta, Sauer, Sebastian, Schlichting, Moritz, Seoane, Jose A., Serra, Jordi, Shang, Ming-Mei, Sharma, Alok, Sharma, Hari, Shen, Yang, Shiga, Motoki, Shin, Moonshik, Shkedy, Ziv, Shopsowitz, Kevin, Sinai, Sam, Skola, Dylan, Smirnov, Petr, Soerensen, Izel Fourie, Soerensen, Peter, Song, Je-Hoon, Song, Sang Ok, Soufan, Othman, Spitzmueller, Andreas, Steipe, Boris, Suphavilai, Chayaporn, Tamayo, Sergio Pulido, Tamborero, David, Tang, Jing, Tanoli, Zia-ur-Rehman, Tarres-Deulofeu, Marc, Tegner, Jesper, Thommesen, Liv, Tonekaboni, Seyed Ali Madani, Tran, Hong T., De Troyer, Ewoud, Truong, Amy, Tsunoda, Tatsuhiko, Turu, Gabor, Tzeng, Guang-Yo, Verbeke, Lieven, Videla, Santiago, Vis, Daniel, Voronkov, Andrey, Votis, Konstantinos, Wang, Ashley, Wang, Hong-Qiang Horace, Wang, Po-Wei, Wang, Sheng, Wang, Wei, Wang, Xiaochen, Wang, Xin, Wennerberg, Krister, Wernisch, Lorenz, Wessels, Lodewyk, van Westen, Gerard J. P., Westerman, Bart A., White, Simon Richard, Willighagen, Egon, Wurdinger, Tom, Xie, Lei, Xie, Shuilian, Xu, Hua, Yadav, Bhagwan, Yau, Christopher, Yeerna, Huwate, Yin, Jia Wei, Yu, Michael, Yu, MinHwan, Yun, So Jeong, Zakharov, Alexey, Zamichos, Alexandros, Zanin, Massimiliano, Zeng, Li, Zenil, Hector, Zhang, Frederick, Zhang, Pengyue, Zhang, Wei, Zhao, Hongyu, Zhao, Lan, Zheng, Wenjin, Zoufir, Azedine, Zucknick, Manuela, Computer Science, Menden, Michael P., Wang, Dennis, Mason, Mike J., Szalai, Bence, Bulusu, Krishna C., Guan, Yuanfang, Yu, Thomas, Kang, Jaewoo, Jeon, Minji, Wolfinger, Russ, Nguyen, Tin, Zaslavskiy, Mikhail, Jang, In Sock, Ghazoui, Zara, Ahsen, Mehmet Eren, Vogel, Robert, Neto, Elias Chaibub, Norman, Thea, Tang, Eric K. Y., Garnett, Mathew J., Di Veroli, Giovanni Y., Fawell, Stephen, Stolovitzky, Gustavo, Guinney, Justin, Dry, Jonathan R., Saez-Rodriguez, Julio, Abante, Jordi, Abecassis, Barbara Schmitz, Aben, Nanne, Aghamirzaie, Delasa, Aittokallio, Tero, Akhtari, Farida S., Al-lazikani, Bissan, Alam, Tanvir, Allam, Amin, Allen, Chad, de Almeida, Mariana Pelicano, Altarawy, Doaa, Alves, Vinicius, Amadoz, Alicia, Anchang, Benedict, Antolin, Albert A., Ash, Jeremy R., Romeo Aznar, Victoria, Ba-alawi, Wail, Bagheri, Moeen, Bajic, Vladimir, Ball, Gordon, Ballester, Pedro J., Baptista, Delora, Bare, Christopher, Bateson, Mathilde, Bender, Andreas, Bertrand, Denis, Wijayawardena, Bhagya, Boroevich, Keith A., Bosdriesz, Evert, Bougouffa, Salim, Bounova, Gergana, Brouwer, Thomas, Bryant, Barbara, Calaza, Manuel, Calderone, Alberto, Calza, Stefano, Capuzzi, Stephen, Carbonell-Caballero, Jose, Carlin, Daniel, Carter, Hannah, Castagnoli, Luisa, Celebi, Remzi, Cesareni, Gianni, Chang, Hyeokyoon, Chen, Guocai, Chen, Haoran, Chen, Huiyuan, Cheng, Lijun, Chernomoretz, Ariel, Chicco, Davide, Cho, Kwang-Hyun, Cho, Sunghwan, Choi, Daeseon, Choi, Jaejoon, Choi, Kwanghun, Choi, Minsoo, De Cock, Martine, Coker, Elizabeth, Cortes-Ciriano, Isidro, Cserzo, Miklos, Cubuk, Cankut, Curtis, Christina, Van Daele, Dries, Dang, Cuong C., Dijkstra, Tjeerd, Dopazo, Joaquin, Draghici, Sorin, Drosou, Anastasios, Dumontier, Michel, Ehrhart, Friederike, Eid, Fatma-Elzahraa, ElHefnawi, Mahmoud, Elmarakeby, Haitham A., van Engelen, Bo, Engin, Hatice Billur, de Esch, Iwan, Evelo, Chris, Falcao, Andre O., Farag, Sherif, Fernandez-Lozano, Carlos, Fisch, Kathleen, Flobak, Asmund, Fornari, Chiara, Foroushani, Amir B. K., Fotso, Donatien Chedom, Fourches, Denis, Friend, Stephen, Frigessi, Arnoldo, Gao, Feng, Gao, Xiaoting, Gerold, Jeffrey M., Gestraud, Pierre, Ghosh, Samik, Gillberg, Jussi, Godoy-Lorite, Antonia, Godynyuk, Lizzy, Godzik, Adam, Goldenberg, Anna, Gomez-Cabrero, David, Gonen, Mehmet, de Graaf, Chris, Gray, Harry, Grechkin, Maxim, Guimera, Roger, Guney, Emre, Haibe-Kains, Benjamin, Han, Younghyun, Hase, Takeshi, He, Di, He, Liye, Heath, Lenwood S., Hellton, Kristoffer H., Helmer-Citterich, Manuela, Hidalgo, Marta R., Hidru, Daniel, Hill, Steven M., Hochreiter, Sepp, Hong, Seungpyo, Hovig, Eivind, Hsueh, Ya-Chih, Hu, Zhiyuan, Huang, Justin K., Huang, R. Stephanie, Hunyady, Laszlo, Hwang, Jinseub, Hwang, Tae Hyun, Hwang, Woochang, Hwang, Yongdeuk, Isayev, Olexandr, Walk, Oliver Bear Don't, Jack, John, Jahandideh, Samad, Ji, Jiadong, Jo, Yousang, Kamola, Piotr J., Kanev, Georgi K., Karacosta, Loukia, Karimi, Mostafa, Kaski, Samuel, Kazanov, Marat, Khamis, Abdullah M., Khan, Suleiman Ali, Kiani, Narsis A., Kim, Allen, Kim, Jinhan, Kim, Juntae, Kim, Kiseong, Kim, Kyung, Kim, Sunkyu, Kim, Yongsoo, Kim, Yunseong, Kirk, Paul D. W., Kitano, Hiroaki, Klambauer, Gunter, Knowles, David, Ko, Melissa, Kohn-Luque, Alvaro, Kooistra, Albert J., Kuenemann, Melaine A., Kuiper, Martin, Kurz, Christoph, Kwon, Mijin, van Laarhoven, Twan, Laegreid, Astrid, Lederer, Simone, Lee, Heewon, Lee, Jeon, Lee, Yun Woo, Leppaho, Eemeli, Lewis, Richard, Li, Jing, Li, Lang, Liley, James, Lim, Weng Khong, Lin, Chieh, Liu, Yiyi, Lopez, Yosvany, Low, Joshua, Lysenko, Artem, Machado, Daniel, Madhukar, Neel, De Maeyer, Dries, Malpartida, Ana Belen, Mamitsuka, Hiroshi, Marabita, Francesco, Marchal, Kathleen, Marttinen, Pekka, Mason, Daniel, Mazaheri, Alireza, Mehmood, Arfa, Mehreen, Ali, Michaut, Magali, Miller, Ryan A., Mitsopoulos, Costas, Modos, Dezso, Van Moerbeke, Marijke, Moo, Keagan, Motsinger-Reif, Alison, Movva, Rajiv, Muraru, Sebastian, Muratov, Eugene, Mushthofa, Mushthofa, Nagarajan, Niranjan, Nakken, Sigve, Nath, Aritro, Neuvial, Pierre, Newton, Richard, Ning, Zheng, De Niz, Carlos, Oliva, Baldo, Olsen, Catharina, Palmeri, Antonio, Panesar, Bhawan, Papadopoulos, Stavros, Park, Jaesub, Park, Seonyeong, Park, Sungjoon, Pawitan, Yudi, Peluso, Daniele, Pendyala, Sriram, Peng, Jian, Perfetto, Livia, Pirro, Stefano, Plevritis, Sylvia, Politi, Regina, Poon, Hoifung, Porta, Eduard, Prellner, Isak, Preuer, Kristina, Angel Pujana, Miguel, Ramnarine, Ricardo, Reid, John E., Reyal, Fabien, Richardson, Sylvia, Ricketts, Camir, Rieswijk, Linda, Rocha, Miguel, Rodriguez-Gonzalvez, Carmen, Roell, Kyle, Rotroff, Daniel, de Ruiter, Julian R., Rukawa, Ploy, Sadacca, Benjamin, Safikhani, Zhaleh, Safitri, Fita, Sales-Pardo, Marta, Sauer, Sebastian, Schlichting, Moritz, Seoane, Jose A., Serra, Jordi, Shang, Ming-Mei, Sharma, Alok, Sharma, Hari, Shen, Yang, Shiga, Motoki, Shin, Moonshik, Shkedy, Ziv, Shopsowitz, Kevin, Sinai, Sam, Skola, Dylan, Smirnov, Petr, Soerensen, Izel Fourie, Soerensen, Peter, Song, Je-Hoon, Song, Sang Ok, Soufan, Othman, Spitzmueller, Andreas, Steipe, Boris, Suphavilai, Chayaporn, Tamayo, Sergio Pulido, Tamborero, David, Tang, Jing, Tanoli, Zia-ur-Rehman, Tarres-Deulofeu, Marc, Tegner, Jesper, Thommesen, Liv, Tonekaboni, Seyed Ali Madani, Tran, Hong T., De Troyer, Ewoud, Truong, Amy, Tsunoda, Tatsuhiko, Turu, Gabor, Tzeng, Guang-Yo, Verbeke, Lieven, Videla, Santiago, Vis, Daniel, Voronkov, Andrey, Votis, Konstantinos, Wang, Ashley, Wang, Hong-Qiang Horace, Wang, Po-Wei, Wang, Sheng, Wang, Wei, Wang, Xiaochen, Wang, Xin, Wennerberg, Krister, Wernisch, Lorenz, Wessels, Lodewyk, van Westen, Gerard J. P., Westerman, Bart A., White, Simon Richard, Willighagen, Egon, Wurdinger, Tom, Xie, Lei, Xie, Shuilian, Xu, Hua, Yadav, Bhagwan, Yau, Christopher, Yeerna, Huwate, Yin, Jia Wei, Yu, Michael, Yu, MinHwan, Yun, So Jeong, Zakharov, Alexey, Zamichos, Alexandros, Zanin, Massimiliano, Zeng, Li, Zenil, Hector, Zhang, Frederick, Zhang, Pengyue, Zhang, Wei, Zhao, Hongyu, Zhao, Lan, Zheng, Wenjin, Zoufir, Azedine, and Zucknick, Manuela

Abstract

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.

Published
2019

36. Inferring causal molecular networks: empirical assessment through a community-based effort

Author

Hill, Steven M., Heiser, Laura M., Cokelaer, Thomas, Unger, Michael, Nesser, Nicole K., Carlin, Daniel E., Zhang, Yang, Sokolov, Artem, Paull, Evan O., Wong, Chris K., Graim, Kiley, Bivol, Adrian, Wang, Haizhou, Zhu, Fan, Afsari, Bahman, and Koeppl, Heinz

Abstract

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense., Nature Methods, 13 (4), ISSN:1548-7105, ISSN:1548-7091

Published
2016
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39. A Villa of Your Own--for a Week; Thanks to the Internet, European vacation rentals from Tuscany to the Costa Brava are easier to find from afar

Author

Matlack, Carol and Carlin, Daniel

Subjects
Market trend/market analysis, Company business management, Online travel service, Online travel services -- Forecasts and trends, Online travel services -- Usage, Travel industry -- Management, Travel industry -- Methods, Package tours -- Management, Package tours -- Forecasts and trends
Published
2007

40. Abstract 3882: Patient-specific druggable networks in lethal prostate cancer through proteome-guided multi-omic integration

Author

Drake, Justin M., primary, Paull, Evan O., additional, Graham, Nicholas A., additional, Lee, John K., additional, Smith, Bryan A., additional, Stoyanova, Tanya, additional, Faltermeier, Claire M., additional, Carlin, Daniel E., additional, Vashisht, Ajay, additional, Huang, Jiaoti, additional, Wohlschlegel, James A., additional, Graeber, Thomas G., additional, Witte, Owen N., additional, and Stuart, Joshua M., additional

Published
2016
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42. BACK TO SCHOOL 2020.

Author

Carlin, Daniel

Abstract

The article discusses that Dr. Daniel Carlin, who has provided tips on how you can reduce your child's risk while going back to school. Topics discussed include trying to stop that will likely be a fools errand, but reducing to some extent will help to reduce risk; and increasingly, authorities are saying that surfaces play less of a role than originally thought, that doesn't mean to ignore surfaces, but people, including kids, should not feel like every time they touch.

Published
2020

43. The Somatic Genomic Landscape of Glioblastoma

Author

Brennan, Cameron W., primary, Verhaak, Roel G.W., additional, McKenna, Aaron, additional, Campos, Benito, additional, Noushmehr, Houtan, additional, Salama, Sofie R., additional, Zheng, Siyuan, additional, Chakravarty, Debyani, additional, Sanborn, J. Zachary, additional, Berman, Samuel H., additional, Beroukhim, Rameen, additional, Bernard, Brady, additional, Wu, Chang-Jiun, additional, Genovese, Giannicola, additional, Shmulevich, Ilya, additional, Barnholtz-Sloan, Jill, additional, Zou, Lihua, additional, Vegesna, Rahulsimham, additional, Shukla, Sachet A., additional, Ciriello, Giovanni, additional, Yung, W.K., additional, Zhang, Wei, additional, Sougnez, Carrie, additional, Mikkelsen, Tom, additional, Aldape, Kenneth, additional, Bigner, Darell D., additional, Van Meir, Erwin G., additional, Prados, Michael, additional, Sloan, Andrew, additional, Black, Keith L., additional, Eschbacher, Jennifer, additional, Finocchiaro, Gaetano, additional, Friedman, William, additional, Andrews, David W., additional, Guha, Abhijit, additional, Iacocca, Mary, additional, O’Neill, Brian P., additional, Foltz, Greg, additional, Myers, Jerome, additional, Weisenberger, Daniel J., additional, Penny, Robert, additional, Kucherlapati, Raju, additional, Perou, Charles M., additional, Hayes, D. Neil, additional, Gibbs, Richard, additional, Marra, Marco, additional, Mills, Gordon B., additional, Lander, Eric, additional, Spellman, Paul, additional, Wilson, Richard, additional, Sander, Chris, additional, Weinstein, John, additional, Meyerson, Matthew, additional, Gabriel, Stacey, additional, Laird, Peter W., additional, Haussler, David, additional, Getz, Gad, additional, Chin, Lynda, additional, Benz, Christopher, additional, Barrett, Wendi, additional, Ostrom, Quinn, additional, Wolinsky, Yingli, additional, Bose, Bikash, additional, Boulos, Paul T., additional, Boulos, Madgy, additional, Brown, Jenn, additional, Czerinski, Christine, additional, Eppley, Matthew, additional, Kempista, Thelma, additional, Kitko, Teresa, additional, Koyfman, Yakov, additional, Rabeno, Brenda, additional, Rastogi, Pawan, additional, Sugarman, Michael, additional, Swanson, Patricia, additional, Yalamanchii, Kennedy, additional, Otey, Ilana P., additional, Liu, Yingchun Spring, additional, Xiao, Yonghong, additional, Auman, J.Todd, additional, Chen, Peng-Chieh, additional, Hadjipanayis, Angela, additional, Lee, Eunjung, additional, Lee, Semin, additional, Park, Peter J., additional, Seidman, Jonathan, additional, Yang, Lixing, additional, Kalkanis, Steven, additional, Poisson, Laila M., additional, Raghunathan, Aditya, additional, Scarpace, Lisa, additional, Bressler, Ryan, additional, Eakin, Andrea, additional, Iype, Lisa, additional, Kreisberg, Richard B., additional, Leinonen, Kalle, additional, Reynolds, Sheila, additional, Rovira, Hector, additional, Thorsson, Vesteinn, additional, Annala, Matti J., additional, Paulauskis, Joseph, additional, Curley, Erin, additional, Hatfield, Martha, additional, Mallery, David, additional, Morris, Scott, additional, Shelton, Troy, additional, Shelton, Candace, additional, Sherman, Mark, additional, Yena, Peggy, additional, Cuppini, Lucia, additional, DiMeco, Francesco, additional, Eoli, Marica, additional, Maderna, Emanuela, additional, Pollo, Bianca, additional, Saini, Marco, additional, Balu, Saianand, additional, Hoadley, Katherine A., additional, Li, Ling, additional, Miller, C. Ryan, additional, Shi, Yan, additional, Topal, Michael D., additional, Wu, Junyuan, additional, Dunn, Gavin, additional, Giannini, Caterina, additional, O'Neill, Brian P., additional, Aksoy, B. Arman, additional, Antipin, Yevgeniy, additional, Borsu, Laetitia, additional, Brennan, Cameron W., additional, Cerami, Ethan, additional, Gao, Jianjiong, additional, Gross, Benjamin, additional, Jacobsen, Anders, additional, Ladanyi, Marc, additional, Lash, Alex, additional, Liang, Yupu, additional, Reva, Boris, additional, Schultz, Nikolaus, additional, Shen, Ronglai, additional, Socci, Nicholas D., additional, Viale, Agnes, additional, Ferguson, Martin L., additional, Chen, Qing-Rong, additional, Demchok, John A., additional, Dillon, Laura A.L., additional, Shaw, Kenna R. Mills, additional, Sheth, Margi, additional, Tarnuzzer, Roy, additional, Wang, Zhining, additional, Yang, Liming, additional, Davidsen, Tanja, additional, Guyer, Mark S., additional, Ozenberger, Bradley A., additional, Sofia, Heidi J., additional, Bergsten, Julie, additional, Eckman, John, additional, Harr, Jodi, additional, Smith, Christine, additional, Tucker, Kelly, additional, Winemiller, Cindy, additional, Zach, Leigh Anne, additional, Ljubimova, Julia Y., additional, Eley, Greg, additional, Ayala, Brenda, additional, Jensen, Mark A., additional, Kahn, Ari, additional, Pihl, Todd D., additional, Pot, David A., additional, Wan, Yunhu, additional, Hansen, Nathan, additional, Hothi, Parvi, additional, Lin, Biaoyang, additional, Shah, Nameeta, additional, Yoon, Jae-geun, additional, Lau, Ching, additional, Berens, Michael, additional, Ardlie, Kristin, additional, Carter, Scott L., additional, Cherniack, Andrew D., additional, Noble, Mike, additional, Cho, Juok, additional, Cibulskis, Kristian, additional, DiCara, Daniel, additional, Frazer, Scott, additional, Gabriel, Stacey B., additional, Gehlenborg, Nils, additional, Gentry, Jeff, additional, Heiman, David, additional, Kim, Jaegil, additional, Jing, Rui, additional, Lander, Eric S., additional, Lawrence, Michael, additional, Lin, Pei, additional, Mallard, Will, additional, Onofrio, Robert C., additional, Saksena, Gordon, additional, Schumacher, Steve, additional, Stojanov, Petar, additional, Tabak, Barbara, additional, Voet, Doug, additional, Zhang, Hailei, additional, Dees, Nathan N., additional, Ding, Li, additional, Fulton, Lucinda L., additional, Fulton, Robert S., additional, Kanchi, Krishna-Latha, additional, Mardis, Elaine R., additional, Wilson, Richard K., additional, Baylin, Stephen B., additional, Harshyne, Larry, additional, Cohen, Mark L., additional, Devine, Karen, additional, Sloan, Andrew E., additional, VandenBerg, Scott R., additional, Berger, Mitchel S., additional, Carlin, Daniel, additional, Craft, Brian, additional, Ellrott, Kyle, additional, Goldman, Mary, additional, Goldstein, Theodore, additional, Grifford, Mia, additional, Ma, Singer, additional, Ng, Sam, additional, Stuart, Joshua, additional, Swatloski, Teresa, additional, Waltman, Peter, additional, Zhu, Jing, additional, Foss, Robin, additional, Frentzen, Barbara, additional, McTiernan, Raquel, additional, Yachnis, Anthony, additional, Mao, Yong, additional, Akbani, Rehan, additional, Bogler, Oliver, additional, Fuller, Gregory N., additional, Liu, Wenbin, additional, Liu, Yuexin, additional, Lu, Yiling, additional, Mills, Gordon, additional, Protopopov, Alexei, additional, Ren, Xiaojia, additional, Sun, Youting, additional, Yung, W.K. Alfred, additional, Zhang, Jianhua, additional, Chen, Ken, additional, Weinstein, John N., additional, Bootwalla, Moiz S., additional, Lai, Phillip H., additional, Triche, Timothy J., additional, Van Den Berg, David J., additional, Gutmann, David H., additional, Lehman, Norman L., additional, VanMeir, Erwin G., additional, Brat, Daniel, additional, Olson, Jeffrey J., additional, Mastrogianakis, Gena M., additional, Devi, Narra S., additional, Zhang, Zhaobin, additional, Bigner, Darell, additional, Lipp, Eric, additional, and McLendon, Roger, additional

Published
2013
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45. The origin of islet-like cells in Drosophila identifies parallels to the vertebrate endocrine axis.

Author

Shu Wang, Tulina, Natalia, Carlin, Daniel L., and Rulifson, Eric J.

Subjects
GLUCAGON, INSULIN, NEUROBLASTOMA, PITUITARY gland, HYPOTHALAMUS
Abstract

Single-cell resolution lineage information is a critical key to understanding how the states of gene regulatory networks respond to cell interactions and thereby establish distinct cell fates. Here, we identify a single pair of neural stem cells (neuroblasts) as progenitors of the brain insulin-producing neurosecretory cells of Drosophila, which are homologous to islet β cells. Likewise, we identify a second pair of neuroblasts as progenitors of the neurosecretory Corpora cardiaca cells, which are homologous to the glucagon-secreting islet a cells. We find that both progenitors originate as neighboring cells from anterior neuroectoderm, which expresses genes orthologous to those expressed in the vertebrate adenohypophyseal placode, the source of endocrine anterior pituitary and neurosecretory hypothalamic cells [Whitlock KE (2005) Trends Endocrinol Metab 16:145-151]. This ontogenic-molecular concordance suggests that a rudimentary brain endocrine axis was present in the common ancestor of humans and flies, where it orchestrated the islet-like endocrine functions of insulin and glucagon biology. [ABSTRACT FROM AUTHOR]

Published
2007
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46. Taxpayers foot bill as electric cars charged for free at Commons.

Author

Brendan Carlin ; Daniel Jones

Abstract

MPs are charging their car batteries at the Palace of Westminster on the public purse - even as Ministers consider whether to hike petrol duties, The Mail on Sunday can reveal. [ABSTRACT FROM PUBLISHER]

Published
2022

47. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Author

Menden, Michael P., Wang, Dennis, Mason, Mike J., Szalai, Bence, Bulusu, Krishna C., Guan, Yuanfang, Yu, Thomas, Kang, Jaewoo, Jeon, Minji, Wolfinger, Russ, Nguyen, Tin, Zaslavskiy, Mikhail, Jang, In Sock, Ghazoui, Zara, Ahsen, Mehmet Eren, Vogel, Robert, Neto, Elias Chaibub, Norman, Thea, Tang, Eric K. Y., Garnett, Mathew J., Veroli, Giovanni Y. Di, Fawell, Stephen, Stolovitzky, Gustavo, Guinney, Justin, Dry, Jonathan R., Saez-Rodriguez, Julio, Abante, Jordi, Abecassis, Barbara Schmitz, Aben, Nanne, Aghamirzaie, Delasa, Aittokallio, Tero, Akhtari, Farida S., Al-Lazikani, Bissan, Alam, Tanvir, Allam, Amin, Allen, Chad, De Almeida, Mariana Pelicano, Altarawy, Doaa, Alves, Vinicius, Amadoz, Alicia, Anchang, Benedict, Antolin, Albert A., Ash, Jeremy R., Aznar, Victoria Romeo, Ba-Alawi, Wail, Bagheri, Moeen, Bajic, Vladimir, Ball, Gordon, Ballester, Pedro J., Baptista, Delora, Bare, Christopher, Bateson, Mathilde, Bender, Andreas, Bertrand, Denis, Wijayawardena, Bhagya, Boroevich, Keith A., Bosdriesz, Evert, Bougouffa, Salim, Bounova, Gergana, Brouwer, Thomas, Bryant, Barbara, Calaza, Manuel, Calderone, Alberto, Calza, Stefano, Capuzzi, Stephen, Carbonell-Caballero, Jose, Carlin, Daniel, Carter, Hannah, Castagnoli, Luisa, Celebi, Remzi, Cesareni, Gianni, Chang, Hyeokyoon, Chen, Guocai, Chen, Haoran, Chen, Huiyuan, Cheng, Lijun, Chernomoretz, Ariel, Chicco, Davide, Cho, Kwang-Hyun, Cho, Sunghwan, Choi, Daeseon, Choi, Jaejoon, Choi, Kwanghun, Choi, Minsoo, Cock, Martine De, Coker, Elizabeth, Cortes-Ciriano, Isidro, Cserzö, Miklós, Cubuk, Cankut, Curtis, Christina, Daele, Dries Van, Dang, Cuong C., Dijkstra, Tjeerd, Dopazo, Joaquin, Draghici, Sorin, Drosou, Anastasios, Dumontier, Michel, Ehrhart, Friederike, Eid, Fatma-Elzahraa, ElHefnawi, Mahmoud, Elmarakeby, Haitham, Van Engelen, Bo, Engin, Hatice Billur, De Esch, Iwan, Evelo, Chris, Falcao, Andre O., Farag, Sherif, Fernandez-Lozano, Carlos, Fisch, Kathleen, Flobak, Asmund, Fornari, Chiara, Foroushani, Amir B. K., Fotso, Donatien Chedom, Fourches, Denis, Friend, Stephen, Frigessi, Arnoldo, Gao, Feng, Gao, Xiaoting, Gerold, Jeffrey M., Gestraud, Pierre, Ghosh, Samik, Gillberg, Jussi, Godoy-Lorite, Antonia, Godynyuk, Lizzy, Godzik, Adam, Goldenberg, Anna, Gomez-Cabrero, David, Gonen, Mehmet, De Graaf, Chris, Gray, Harry, Grechkin, Maxim, Guimera, Roger, Guney, Emre, Haibe-Kains, Benjamin, Han, Younghyun, Hase, Takeshi, He, Di, He, Liye, Heath, Lenwood S., Hellton, Kristoffer H., Helmer-Citterich, Manuela, Hidalgo, Marta R., Hidru, Daniel, Hill, Steven M., Hochreiter, Sepp, Hong, Seungpyo, Hovig, Eivind, Hsueh, Ya-Chih, Hu, Zhiyuan, Huang, Justin K, Huang, R. Stephanie, Hunyady, László, Hwang, Jinseub, Hwang, Tae Hyun, Hwang, Woochang, Hwang, Yongdeuk, Isayev, Olexandr, Don’t Walk, Oliver Bear, Jack, John, Jahandideh, Samad, Ji, Jiadong, Jo, Yousang, Kamola, Piotr J., Kanev, Georgi K., Karacosta, Loukia, Karimi, Mostafa, Kaski, Samuel, Kazanov, Marat, Khamis, Abdullah M, Khan, Suleiman Ali, Kiani, Narsis A., Kim, Allen, Kim, Jinhan, Kim, Juntae, Kim, Kiseong, Kim, Kyung, Kim, Sunkyu, Kim, Yongsoo, Kim, Yunseong, Kirk, Paul D. W., Kitano, Hiroaki, Klambauer, Gunter, Knowles, David, Ko, Melissa, Kohn-Luque, Alvaro, Kooistra, Albert J., Kuenemann, Melaine A., Kuiper, Martin, Kurz, Christoph, Kwon, Mijin, Van Laarhoven, Twan, Laegreid, Astrid, Lederer, Simone, Lee, Heewon, Lee, Jeon, Lee, Yun Woo, Lepp_aho, Eemeli, Lewis, Richard, Li, Jing, Li, Lang, Liley, James, Lim, Weng Khong, Lin, Chieh, Liu, Yiyi, Lopez, Yosvany, Low, Joshua, Lysenko, Artem, Machado, Daniel, Madhukar, Neel, Maeyer, Dries De, Malpartida, Ana Belen, Mamitsuka, Hiroshi, Marabita, Francesco, Marchal, Kathleen, Marttinen, Pekka, Mason, Daniel, Mazaheri, Alireza, Mehmood, Arfa, Mehreen, Ali, Michaut, Magali, Miller, Ryan A., Mitsopoulos, Costas, Modos, Dezso, Moerbeke, Marijke Van, Moo, Keagan, Motsinger-Reif, Alison, Movva, Rajiv, Muraru, Sebastian, Muratov, Eugene, Mushthofa, Mushthofa, Nagarajan, Niranjan, Nakken, Sigve, Nath, Aritro, Neuvial, Pierre, Newton, Richard, Ning, Zheng, Niz, Carlos De, Oliva, Baldo, Olsen, Catharina, Palmeri, Antonio, Panesar, Bhawan, Papadopoulos, Stavros, Park, Jaesub, Park, Seonyeong, Park, Sungjoon, Pawitan, Yudi, Peluso, Daniele, Pendyala, Sriram, Peng, Jian, Perfetto, Livia, Pirro, Stefano, Plevritis, Sylvia, Politi, Regina, Poon, Hoifung, Porta, Eduard, Prellner, Isak, Preuer, Kristina, Pujana, Miguel Angel, Ramnarine, Ricardo, Reid, John E., Reyal, Fabien, Richardson, Sylvia, Ricketts, Camir, Rieswijk, Linda, Rocha, Miguel, Rodriguez-Gonzalvez, Carmen, Roell, Kyle, Rotroff, Daniel, De Ruiter, Julian R., Rukawa, Ploy, Sadacca, Benjamin, Safikhani, Zhaleh, Safitri, Fita, Sales-Pardo, Marta, Sauer, Sebastian, Schlichting, Moritz, Seoane, Jose A., Serra, Jordi, Shang, Ming-Mei, Sharma, Alok, Sharma, Hari, Shen, Yang, Shiga, Motoki, Shin, Moonshik, Shkedy, Ziv, Shopsowitz, Kevin, Sinai, Sam, Skola, Dylan, Smirnov, Petr, Soerensen, Izel Fourie, Soerensen, Peter, Song, Je-Hoon, Song, Sang Ok, Soufan, Othman, Spitzmueller, Andreas, Steipe, Boris, Suphavilai, Chayaporn, Tamayo, Sergio Pulido, Tamborero, David, Tang, Jing, Tanoli, Zia-Ur-Rehman, Tarres-Deulofeu, Marc, Tegner, Jesper, Thommesen, Liv, Tonekaboni, Seyed Ali Madani, Tran, Hong, Troyer, Ewoud De, Truong, Amy, Tsunoda, Tatsuhiko, Turu, Gábor, Tzeng, Guang-Yo, Verbeke, Lieven, Videla, Santiago, Vis, Daniel, Voronkov, Andrey, Votis, Konstantinos, Wang, Ashley, Wang, Hong-Qiang Horace, Wang, Po-Wei, Wang, Sheng, Wang, Wei, Wang, Xiaochen, Wang, Xin, Wennerberg, Krister, Wernisch, Lorenz, Wessels, Lodewyk, Van Westen, Gerard J. P., Westerman, Bart A., White, Simon Richard, Willighagen, Egon, Wurdinger, Tom, Xie, Lei, Xie, Shuilian, Xu, Hua, Yadav, Bhagwan, Yau, Christopher, Yeerna, Huwate, Yin, Jia Wei, Yu, Michael, Yu, MinHwan, Yun, So Jeong, Zakharov, Alexey, Zamichos, Alexandros, Zanin, Massimiliano, Zeng, Li, Zenil, Hector, Zhang, Frederick, Zhang, Pengyue, Zhang, Wei, Zhao, Hongyu, Zhao, Lan, Zheng, Wenjin, Zoufir, Azedine, and Zucknick, Manuela

Subjects
49/98, 45, 49/23, article, 49/39, 631/553, 631/114/1305, 631/114/2415, 631/154/1435/2163, 692/4028/67, 13, 3. Good health, 49
Abstract

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.

48. Inferring causal molecular networks: empirical assessment through a community-based effort

Author

Carlin, Daniel E., Hill, Steven M., Meerzaman, Daoud, Kannan, Venkateshan, Afsari, Bahman, Hase, Takeshi, Budak, Gungor, Lee, Wai Shing, Caglar, Mehmet, Stuart, Joshua M., Coort, Susan, Haider, Saad, Friend, Stephen, Carlon, Azzurra, Zairis, Sakellarios, Cai, Binghuang, Sichani, Omid Askari, Komatsoulis, George, Sambo, Francesco, Kursa, Miron Bartosz, Kikuchi, Kaito, Nesser, Nicole K., Anton, Bernat, Wang, Haizhou, Huang, Xun, Bonneau, Richard, Knapp, Bettina, Berlow, Noah, Wan, Qian, Graim, Kiley, Paull, Evan O., Guan, Yuanfang, Gao, Xi, Lu, Songjian, Trifoglio, Emanuele, Neapolitan, Richard E., Hafemeister, Christoph, Finotello, Francesca, Linger, Michael, Bonet, Jaume, Saez-Rodriguez, Julio, Zhang, Yang, Zi, Zhike, Min, Wenwen, Al-Ouran, Rami, Giaretta, Alberto, Strunz, Sonja, Bagheri, Neda, Di Camillo, Barbara, Bohler, Anwesha, Hu, Ying, Creighton, Chad J., Poglayen, Daniel, Song, Mingzhou, Ghosh, Samik, Kaderali, Lars, Arodz, Tomasz, Evelo, Chris, Bivol, Adrian, Kitano, Hiroaki, Zengerling, Michael, Qutub, Amina A., Pal, Ranadip, Sanavia, Tiziana, Xue, Albert Y., Liu, Yu, Cokelaer, Thomas, Gray, Joe W., Mills, Gordon B., Fertig, Elana J., Palinkas, Aljoscha, Tegnér, Jesper, Li, Yichao, Chen, Lujia, Mukherjee, Sach, Emmett, Kevin, Hodgson, Jay, Jiang, Xia, Oliva, Baldo, Yamanaka, Ryota, Yan, Chunhua, Spellman, Paul T., Welch, Lonnie, Großeholz, Ruth, Kellen, Michael, Sharifi-Zarchi, Ali, Ciaccio, Mark F., Guinney, Justin, Thobe, Kirste, Norman, Thea, Zenil, Hector, Hu, Chenyue W., Krämer, Andreas, Cooper, Gregory, Taylor, Dane, Bisberg, Alexander J., Long, Byron L., Streck, Adam, Kacprowski, Tim, Manfrini, Marco, Sokolov, Artem, Jalili, Mahdi, Bunescu, Razvan, Liang, Xiaoyu, Kang, Mingon, Müller, Christian Lorenz, Heiser, Laura M., Zhu, Fan, Hoff, Bruce, Kutmon, Martina, Noren, David P., Dutta-Moscato, Joyeeta, Wong, Chris K., Lu, Xinghua, Favorov, Alexander V., Hahn, Oliver, Finkle, Justin D., Planas-Iglesias, Joan, Liu, Zhaoqi, Fassia, Mohammad-Kasim H., Stolovitzky, Gustavo, Daneshmand, Seyed-Mohammad-Hadi, Unger, Michael, Cai, Chunhui, Koeppl, Heinz, Matos, Marta R. A., Kim, Dong-Chul, Gao, Jean, Hsu, Chih Hao, Danilova, Ludmila V., Toffolo, Gianna Maria, Wu, Jia J., De La Fuente, Alberto, Slawek, Janusz, and Opiyo, Stephen Obol

Subjects
3. Good health
Abstract

Inferring molecular networks is a central challenge in computational biology. However, it has remained unclear whether causal, rather than merely correlational, relationships can be effectively inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge that focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results constitute the most comprehensive assessment of causal network inference in a mammalian setting carried out to date and suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess the causal validity of inferred molecular networks.

49. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Author

Menden, Michael P., Wang, Dennis, Mason, Mike J., Szalai, Bence, Bulusu, Krishna C., Guan, Yuanfang, Yu, Thomas, Kang, Jaewoo, Jeon, Minji, Wolfinger, Russ, Nguyen, Tin, Zaslavskiy, Mikhail, AstraZeneca-Sanger Drug Combination DREAM Consortium, Jang, In Sock, Ghazoui, Zara, Ahsen, Mehmet Eren, Vogel, Robert, Neto, Elias Chaibub, Norman, Thea, Tang, Eric K. Y., Garnett, Mathew J., Di Veroli, Giovanni Y., Fawell, Stephen, Stolovitzky, Gustavo, Guinney, Justin, Dry, Jonathan R., Saez-Rodriguez, Julio, Abante, Jordi, Abecassis, Barbara Schmitz, Aben, Nanne, Aghamirzaie, Delasa, Aittokallio, Tero, Akhtari, Farida S., Al-Lazikani, Bissan, Alam, Tanvir, Allam, Amin, Allen, Chad, De Almeida, Mariana Pelicano, Altarawy, Doaa, Alves, Vinicius, Amadoz, Alicia, Anchang, Benedict, Antolin, Albert A., Ash, Jeremy R., Aznar, Victoria Romeo, Ba-Alawi, Wail, Bagheri, Moeen, Bajic, Vladimir, Ball, Gordon, Ballester, Pedro J., Baptista, Delora, Bare, Christopher, Bateson, Mathilde, Bender, Andreas, Bertrand, Denis, Wijayawardena, Bhagya, Boroevich, Keith A., Bosdriesz, Evert, Bougouffa, Salim, Bounova, Gergana, Brouwer, Thomas, Bryant, Barbara, Calaza, Manuel, Calderone, Alberto, Calza, Stefano, Capuzzi, Stephen, Carbonell-Caballero, Jose, Carlin, Daniel, Carter, Hannah, Castagnoli, Luisa, Celebi, Remzi, Cesareni, Gianni, Chang, Hyeokyoon, Chen, Guocai, Chen, Haoran, Chen, Huiyuan, Cheng, Lijun, Chernomoretz, Ariel, Chicco, Davide, Cho, Kwang-Hyun, Cho, Sunghwan, Choi, Daeseon, Choi, Jaejoon, Choi, Kwanghun, Choi, Minsoo, De Cock, Martine, Coker, Elizabeth, Cortes-Ciriano, Isidro, Cserzö, Miklós, Cubuk, Cankut, Curtis, Christina, Van Daele, Dries, Dang, Cuong C., Dijkstra, Tjeerd, Dopazo, Joaquin, Draghici, Sorin, Drosou, Anastasios, Dumontier, Michel, Ehrhart, Friederike, Eid, Fatma-Elzahraa, ElHefnawi, Mahmoud, Elmarakeby, Haitham, Van Engelen, Bo, Engin, Hatice Billur, De Esch, Iwan, Evelo, Chris, Falcao, Andre O., Farag, Sherif, Fernandez-Lozano, Carlos, Fisch, Kathleen, Flobak, Asmund, Fornari, Chiara, Foroushani, Amir B. K., Fotso, Donatien Chedom, Fourches, Denis, Friend, Stephen, Frigessi, Arnoldo, Gao, Feng, Gao, Xiaoting, Gerold, Jeffrey M., Gestraud, Pierre, Ghosh, Samik, Gillberg, Jussi, Godoy-Lorite, Antonia, Godynyuk, Lizzy, Godzik, Adam, Goldenberg, Anna, Gomez-Cabrero, David, Gonen, Mehmet, De Graaf, Chris, Gray, Harry, Grechkin, Maxim, Guimera, Roger, Guney, Emre, Haibe-Kains, Benjamin, Han, Younghyun, Hase, Takeshi, He, Di, He, Liye, Heath, Lenwood S., Hellton, Kristoffer H., Helmer-Citterich, Manuela, Hidalgo, Marta R., Hidru, Daniel, Hill, Steven M., Hochreiter, Sepp, Hong, Seungpyo, Hovig, Eivind, Hsueh, Ya-Chih, Hu, Zhiyuan, Huang, Justin K., Huang, R. Stephanie, Hunyady, László, Hwang, Jinseub, Hwang, Tae Hyun, Hwang, Woochang, Hwang, Yongdeuk, Isayev, Olexandr, Don't Walk, Oliver Bear, Jack, John, Jahandideh, Samad, Ji, Jiadong, Jo, Yousang, Kamola, Piotr J., Kanev, Georgi K., Karacosta, Loukia, Karimi, Mostafa, Kaski, Samuel, Kazanov, Marat, Khamis, Abdullah M., Khan, Suleiman Ali, Kiani, Narsis A., Kim, Allen, Kim, Jinhan, Kim, Juntae, Kim, Kiseong, Kim, Kyung, Kim, Sunkyu, Kim, Yongsoo, Kim, Yunseong, Kirk, Paul D. W., Kitano, Hiroaki, Klambauer, Gunter, Knowles, David, Ko, Melissa, Kohn-Luque, Alvaro, Kooistra, Albert J., Kuenemann, Melaine A., Kuiper, Martin, Kurz, Christoph, Kwon, Mijin, Van Laarhoven, Twan, Laegreid, Astrid, Lederer, Simone, Lee, Heewon, Lee, Jeon, Lee, Yun Woo, Lepp Aho, Eemeli, Lewis, Richard, Li, Jing, Li, Lang, Liley, James, Lim, Weng Khong, Lin, Chieh, Liu, Yiyi, Lopez, Yosvany, Low, Joshua, Lysenko, Artem, Machado, Daniel, Madhukar, Neel, De Maeyer, Dries, Malpartida, Ana Belen, Mamitsuka, Hiroshi, Marabita, Francesco, Marchal, Kathleen, Marttinen, Pekka, Mason, Daniel, Mazaheri, Alireza, Mehmood, Arfa, Mehreen, Ali, Michaut, Magali, Miller, Ryan A., Mitsopoulos, Costas, Modos, Dezso, Van Moerbeke, Marijke, Moo, Keagan, Motsinger-Reif, Alison, Movva, Rajiv, Muraru, Sebastian, Muratov, Eugene, Mushthofa, Mushthofa, Nagarajan, Niranjan, Nakken, Sigve, Nath, Aritro, Neuvial, Pierre, Newton, Richard, Ning, Zheng, De Niz, Carlos, Oliva, Baldo, Olsen, Catharina, Palmeri, Antonio, Panesar, Bhawan, Papadopoulos, Stavros, Park, Jaesub, Park, Seonyeong, Park, Sungjoon, Pawitan, Yudi, Peluso, Daniele, Pendyala, Sriram, Peng, Jian, Perfetto, Livia, Pirro, Stefano, Plevritis, Sylvia, Politi, Regina, Poon, Hoifung, Porta, Eduard, Prellner, Isak, Preuer, Kristina, Pujana, Miguel Angel, Ramnarine, Ricardo, Reid, John E., Reyal, Fabien, Richardson, Sylvia, Ricketts, Camir, Rieswijk, Linda, Rocha, Miguel, Rodriguez-Gonzalvez, Carmen, Roell, Kyle, Rotroff, Daniel, De Ruiter, Julian R., Rukawa, Ploy, Sadacca, Benjamin, Safikhani, Zhaleh, Safitri, Fita, Sales-Pardo, Marta, Sauer, Sebastian, Schlichting, Moritz, Seoane, Jose A., Serra, Jordi, Shang, Ming-Mei, Sharma, Alok, Sharma, Hari, Shen, Yang, Shiga, Motoki, Shin, Moonshik, Shkedy, Ziv, Shopsowitz, Kevin, Sinai, Sam, Skola, Dylan, Smirnov, Petr, Soerensen, Izel Fourie, Soerensen, Peter, Song, Je-Hoon, Song, Sang Ok, Soufan, Othman, Spitzmueller, Andreas, Steipe, Boris, Suphavilai, Chayaporn, Tamayo, Sergio Pulido, Tamborero, David, Tang, Jing, Tanoli, Zia-Ur-Rehman, Tarres-Deulofeu, Marc, Tegner, Jesper, Thommesen, Liv, Tonekaboni, Seyed Ali Madani, Tran, Hong, De Troyer, Ewoud, Truong, Amy, Tsunoda, Tatsuhiko, Turu, Gábor, Tzeng, Guang-Yo, Verbeke, Lieven, Videla, Santiago, Vis, Daniel, Voronkov, Andrey, Votis, Konstantinos, Wang, Ashley, Wang, Hong-Qiang Horace, Wang, Po-Wei, Wang, Sheng, Wang, Wei, Wang, Xiaochen, Wang, Xin, Wennerberg, Krister, Wernisch, Lorenz, Wessels, Lodewyk, Van Westen, Gerard J. P., Westerman, Bart A., White, Simon Richard, Willighagen, Egon, Wurdinger, Tom, Xie, Lei, Xie, Shuilian, Xu, Hua, Yadav, Bhagwan, Yau, Christopher, Yeerna, Huwate, Yin, Jia Wei, Yu, Michael, Yu, MinHwan, Yun, So Jeong, Zakharov, Alexey, Zamichos, Alexandros, Zanin, Massimiliano, Zeng, Li, Zenil, Hector, Zhang, Frederick, Zhang, Pengyue, Zhang, Wei, Zhao, Hongyu, Zhao, Lan, Zheng, Wenjin, Zoufir, Azedine, and Zucknick, Manuela

Subjects
3. Good health
Abstract

Nat Commun 10(1), 2674 (2019). doi:10.1038/s41467-019-09799-2

50. Rising US star pips Corbyn to Glasto spot.

Author

Brendan Carlin ; Daniel Bates

Abstract

IT was one of the proudest moments of Jeremy Corbyn's career - hearing his name chanted by thousands of fans as he addressed Britain's biggest music festival two years ago. [ABSTRACT FROM PUBLISHER]

Published
2019

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