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3. A Kronecker product accelerated efficient sparse Gaussian Process (E-SGP) for flow emulation

Author

Duan, Yu, Eaton, Matthew, and Bluck, Michael

Subjects
Computer Science - Machine Learning
Abstract

In this paper, we introduce an efficient sparse Gaussian process (E-SGP) for the surrogate modelling of fluid mechanics. This novel Bayesian machine learning algorithm allows efficient model training using databases of different structures. It is a further development of the approximated sparse GP algorithm, combining the concept of efficient GP (E-GP) and variational energy free sparse Gaussian process (VEF-SGP). The developed E-SGP approach exploits the arbitrariness of inducing points and the monotonically increasing nature of the objective function with respect to the number of inducing points in VEF-SGP. By specifying the inducing points on the orthogonal grid/input subspace and using the Kronecker product, E-SGP significantly improves computational efficiency without imposing any constraints on the covariance matrix or increasing the number of parameters that need to be optimised during training. The E-SGP algorithm developed in this paper outperforms E-GP not only in scalability but also in model quality in terms of mean standardized logarithmic loss (MSLL). The computational complexity of E-GP suffers from the cubic growth regarding the growing structured training database. However, E-SGP maintains computational efficiency whilst the resolution of the model, (i.e., the number of inducing points) remains fixed. The examples show that E-SGP produces more accurate predictions in comparison with E-GP when the model resolutions are similar in both. E-GP benefits from more training data but comes with higher computational demands, while E-SGP achieves a comparable level of accuracy but is more computationally efficient, making E-SGP a potentially preferable choice for fluid mechanic problems. Furthermore, E-SGP can produce more reasonable estimates of model uncertainty, whilst E-GP is more likely to produce over-confident predictions.

Published
2023

5. Fixed Inducing Points Online Bayesian Calibration for Computer Models with an Application to a Scale-Resolving CFD Simulation

Author

Duan, Yu, Eaton, Matthew, and Bluck, Michael

Subjects
Physics - Computational Physics, Physics - Data Analysis, Statistics and Probability, Statistics - Machine Learning
Abstract

This paper proposes a novel fixed inducing points online Bayesian calibration (FIPO-BC) algorithm to efficiently learn the model parameters using a benchmark database. The standard Bayesian calibration (STD-BC) algorithm provides a statistical method to calibrate the parameters of computationally expensive models. However, the STD-BC algorithm scales very badly with the number of data points and lacks online learning capability. The proposed FIPO-BC algorithm greatly improves the computational efficiency and enables the online calibration by executing the calibration on a set of predefined inducing points. To demonstrate the procedure of the FIPO-BC algorithm, two tests are performed, finding the optimal value and exploring the posterior distribution of 1) the parameter in a simple function, and 2) the high-wave number damping factor in a scale-resolving turbulence model (SAS-SST). The results (such as the calibrated model parameter and its posterior distribution) of FIPO-BC with different inducing points are compared to those of STD-BC. It is found that FIPO-BC and STD-BC can provide very similar results, once the predefined set of inducing point in FIPO-BC is sufficiently fine. But, the FIPO-BC algorithm is at least ten times faster than the STD-BC algorithm. Meanwhile, the online feature of the FIPO-BC allows continuous updating of the calibration outputs and potentially reduces the workload on generating the database.

Published
2020
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6. Targeting RARA overexpression with tamibarotene, a potent and selective RARα agonist, is a novel approach in AML

Author

de Botton, Stéphane, Cluzeau, Thomas, Vigil, Carlos, Cook, Rachel J., Rousselot, Philippe, Rizzieri, David A., Liesveld, Jane L., Fenaux, Pierre, Braun, Thorsten, Banos, Anne, Jurcic, Joseph G., Sekeres, Mikkael A., Savona, Michael R., Roboz, Gail J., Bixby, Dale, Madigan, Kate, Volkert, Angela, Stephens, Kristin, Kang-Fortner, Qing, Baker, Kristen, Paul, Sofia, McKeown, Michael, Carulli, John, Eaton, Matthew, Hodgson, Graeme, Fiore, Christopher, Kelly, Michael J., Roth, David A., and Stein, Eytan M.

Published
2023
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12. ΔNp63/p73 drive metastatic colonization by controlling a regenerative epithelial stem cell program in quasi-mesenchymal cancer stem cells

Author

Lambert, Arthur W., Fiore, Christopher, Chutake, Yogesh, Verhaar, Elisha R., Strasser, Patrick C., Chen, Mei Wei, Farouq, Daneyal, Das, Sunny, Li, Xin, Eaton, Elinor Ng, Zhang, Yun, Liu Donaher, Joana, Engstrom, Ian, Reinhardt, Ferenc, Yuan, Bingbing, Gupta, Sumeet, Wollison, Bruce, Eaton, Matthew, Bierie, Brian, Carulli, John, Olson, Eric R., Guenther, Matthew G., and Weinberg, Robert A.

Published
2022
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16. Novel epigenomic liquid biopsy assay to predict estrogen receptor (ER) status and to infer ER pathway activation in breast cancer.

Author

Morganti, Stefania, primary, Beagan, Jonathan, additional, D'Ippolito, Anthony, additional, Smith, Kalie, additional, Hughes, Melissa E., additional, Chmielecki, Juliann, additional, Gorthi, Aparna, additional, Painter, Corrie, additional, Barrett, J. Carl, additional, Eaton, Matthew L, additional, Freedman, Matthew, additional, Tolaney, Sara M., additional, Lin, Nancy U., additional, and Parsons, Heather Anne, additional

Published
2024
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20. Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist.

Author

McKeown, Michael, Corces, M, Eaton, Matthew, Fiore, Chris, Lee, Emily, Lopez, Jeremy, Chen, Mei, Smith, Darren, Chan, Steven, Koenig, Julie, Austgen, Kathryn, Guenther, Matthew, Orlando, David, Lovén, Jakob, Fritz, Christian, and Majeti, Ravindra

Subjects
Aged, Animals, Benzoates, Cell Line, Tumor, Cell Proliferation, Cell Survival, Enhancer Elements, Genetic, Epigenomics, Female, Gene Expression Regulation, Neoplastic, High-Throughput Nucleotide Sequencing, Humans, Leukemia, Myeloid, Acute, Mice, Retinoic Acid Receptor alpha, Tetrahydronaphthalenes, Up-Regulation, Xenograft Model Antitumor Assays
Abstract

We characterized the enhancer landscape of 66 patients with acute myeloid leukemia (AML), identifying 6 novel subgroups and their associated regulatory loci. These subgroups are defined by their superenhancer (SE) maps, orthogonal to somatic mutations, and are associated with distinct leukemic cell states. Examination of transcriptional drivers for these epigenomic subtypes uncovers a subset of patients with a particularly strong SE at the retinoic acid receptor alpha (RARA) gene locus. The presence of a RARA SE and concomitant high levels of RARA mRNA predisposes cell lines and ex vivo models to exquisite sensitivity to a selective agonist of RARα, SY-1425 (tamibarotene). Furthermore, only AML patient-derived xenograft (PDX) models with high RARA mRNA were found to respond to SY-1425. Mechanistically, we show that the response to SY-1425 in RARA-high AML cells is similar to that of acute promyelocytic leukemia treated with retinoids, characterized by the induction of known retinoic acid response genes, increased differentiation, and loss of proliferation.Significance: We use the SE landscape of primary human AML to elucidate transcriptional circuitry and identify novel cancer vulnerabilities. A subset of patients were found to have an SE at RARA, which is predictive for response to SY-1425, a potent and selective RARα agonist, in preclinical models, forming the rationale for its clinical investigation in biomarker-selected patients. Cancer Discov; 7(10); 1136-53. ©2017 AACR.See related commentary by Wang and Aifantis, p. 1065.This article is highlighted in the In This Issue feature, p. 1047.

Published
2017

22. Food Ethics and Laudato Sí: An Axiological Approach to Catholic Vegetarianism.

Author

Eaton, Matthew

Subjects
*EFFECT of human beings on climate change, *ENVIRONMENTAL health, *VEGETARIANISM, *HEALTH promotion, *CATHOLICS
Abstract

Pope Francis suggests a vegetarian ethos as a potential response to overcoming anthropogenic climate change. While his motivation is the promotion of ecological health for the sake of human flourishing, this article argues that there is room in Francis' thought for a more expansive vegetarianism that extends its concern beyond humanity to the intrinsic value of Earth and its creatures. Through an analysis of Catholic ecotheology and philosophies of value, this article suggests a pluralistic axiological approach to Catholic vegetarianism, emphasizing the theocentric, anthropocentric, ecocentric, and biocentric value of this concrete initiative aimed at ensuring both divine and creaturely flourishing. [ABSTRACT FROM AUTHOR]

Published
2024
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27. Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci

Author

De Jager, Philip L, Srivastava, Gyan, Lunnon, Katie, Burgess, Jeremy, Schalkwyk, Leonard C, Yu, Lei, Eaton, Matthew L, Keenan, Brendan T, Ernst, Jason, McCabe, Cristin, Tang, Anna, Raj, Towfique, Replogle, Joseph, Brodeur, Wendy, Gabriel, Stacey, Chai, High S, Younkin, Curtis, Younkin, Steven G, Zou, Fanggeng, Szyf, Moshe, Epstein, Charles B, Schneider, Julie A, Bernstein, Bradley E, Meissner, Alex, Ertekin-Taner, Nilufer, Chibnik, Lori B, Kellis, Manolis, Mill, Jonathan, and Bennett, David A

Subjects
Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Alzheimer's Disease, Human Genome, Genetics, Dementia, Neurodegenerative, Acquired Cognitive Impairment, Aging, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adaptor Proteins, Signal Transducing, Aged, Aged, 80 and over, Alzheimer Disease, Amyloidosis, Ankyrins, Brain, Carrier Proteins, CpG Islands, DNA Methylation, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins, Male, Middle Aged, Nuclear Proteins, Protein Interaction Maps, Tumor Suppressor Proteins, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

We used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network.

Published
2014

35. Christian Neoplatonism and Deep Incarnation: Nicholas of Cusa and Giordano Bruno as Inspirations for Contemporary Ecotheology.

Author

Eaton, Matthew

Subjects
*NEOPLATONISM, *INSPIRATION, *ANTHROPOLOGY, *THEOLOGY, *THEOLOGIANS, *INCARNATION, *BREATH holding
Abstract

In response to the specter of looming anthropogenic ecological catastrophe, many Christian thinkers have begun to rethink the God/world relationship and reimagine the ontic cleavage between divinity and creation. The idea of "deep incarnation", which expands the scope of divine incarnation in an attempt to draw God and creation into closer relation, is a prevalent framework for such reimagination. Two historic, underutilized thinkers that might help deep incarnation theologians expand their own theologies and make sense of the conceptual and ethical differences among them are Neo-Platonist philosopher–theologians Nicholas of Cusa and Giordano Bruno. Working within an ecofeminist framework, this article argues that while both Cusanus and Bruno provide significant philosophical grounds for contemporary ecotheologies of deep incarnation, a Brunist perspective is preferable because of its more expansive anthropology and its more inclusive understanding of divinity. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Correction to: DNA copy number evolution in Drosophila cell lines

Author

Lee, Hangnoh, McManus, C. Joel, Cho, Dong-Yeon, Eaton, Matthew, Renda, Fioranna, Somma, Maria Patrizia, Cherbas, Lucy, May, Gemma, Powell, Sara, Zhang, Dayu, Zhan, Lijun, Resch, Alissa, Andrews, Justen, Celniker, Susan E., Cherbas, Peter, Przytycka, Teresa M., Gatti, Maurizio, Oliver, Brian, Graveley, Brenton, and MacAlpine, David

Published
2019
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39. Supplementary Table S3: Median Survival By Cluster from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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40. Supplementary Table S2: mRNA Cluster Signatures from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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41. Supplementary Table S1: Sample mutations from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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42. Supplementary Table S4: Enhancer, mRNA, and SY-1425 EC50 in AML cell lines from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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43. Supplementary Methods and Figure Legends from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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44. Supplementary Table S7: GREAT analysis from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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45. Data from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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46. Supplementary Figures from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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47. Supplementary Table S5 & 6: GSEA of SY-1425 response from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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