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26 results on '"Cheng, Nuojin"'

1. Variational Entropy Search for Adjusting Expected Improvement

Author

Cheng, Nuojin and Becker, Stephen

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning, Mathematics - Optimization and Control
Abstract

Bayesian optimization is a widely used technique for optimizing black-box functions, with Expected Improvement (EI) being the most commonly utilized acquisition function in this domain. While EI is often viewed as distinct from other information-theoretic acquisition functions, such as entropy search (ES) and max-value entropy search (MES), our work reveals that EI can be considered a special case of MES when approached through variational inference (VI). In this context, we have developed the Variational Entropy Search (VES) methodology and the VES-Gamma algorithm, which adapts EI by incorporating principles from information-theoretic concepts. The efficacy of VES-Gamma is demonstrated across a variety of test functions and read datasets, highlighting its theoretical and practical utilities in Bayesian optimization scenarios.

Published
2024

2. Bi-fidelity Variational Auto-encoder for Uncertainty Quantification

Author

Cheng, Nuojin, Malik, Osman Asif, De, Subhayan, Becker, Stephen, and Doostan, Alireza

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning, Mathematics - Numerical Analysis
Abstract

Quantifying the uncertainty of quantities of interest (QoIs) from physical systems is a primary objective in model validation. However, achieving this goal entails balancing the need for computational efficiency with the requirement for numerical accuracy. To address this trade-off, we propose a novel bi-fidelity formulation of variational auto-encoders (BF-VAE) designed to estimate the uncertainty associated with a QoI from low-fidelity (LF) and high-fidelity (HF) samples of the QoI. This model allows for the approximation of the statistics of the HF QoI by leveraging information derived from its LF counterpart. Specifically, we design a bi-fidelity auto-regressive model in the latent space that is integrated within the VAE's probabilistic encoder-decoder structure. An effective algorithm is proposed to maximize the variational lower bound of the HF log-likelihood in the presence of limited HF data, resulting in the synthesis of HF realizations with a reduced computational cost. Additionally, we introduce the concept of the bi-fidelity information bottleneck (BF-IB) to provide an information-theoretic interpretation of the proposed BF-VAE model. Our numerical results demonstrate that BF-VAE leads to considerably improved accuracy, as compared to a VAE trained using only HF data, when limited HF data is available.

Published
2023
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3. Quadrature Sampling of Parametric Models with Bi-fidelity Boosting

Author

Cheng, Nuojin, Malik, Osman Asif, Xu, Yiming, Becker, Stephen, Doostan, Alireza, and Narayan, Akil

Subjects
Mathematics - Numerical Analysis
Abstract

Least squares regression is a ubiquitous tool for building emulators (a.k.a. surrogate models) of problems across science and engineering for purposes such as design space exploration and uncertainty quantification. When the regression data are generated using an experimental design process (e.g., a quadrature grid) involving computationally expensive models, or when the data size is large, sketching techniques have shown promise to reduce the cost of the construction of the regression model while ensuring accuracy comparable to that of the full data. However, random sketching strategies, such as those based on leverage scores, lead to regression errors that are random and may exhibit large variability. To mitigate this issue, we present a novel boosting approach that leverages cheaper, lower-fidelity data of the problem at hand to identify the best sketch among a set of candidate sketches. This in turn specifies the sketch of the intended high-fidelity model and the associated data. We provide theoretical analyses of this bi-fidelity boosting (BFB) approach and discuss the conditions the low- and high-fidelity data must satisfy for a successful boosting. In doing so, we derive a bound on the residual norm of the BFB sketched solution relating it to its ideal, but computationally expensive, high-fidelity boosted counterpart. Empirical results on both manufactured and PDE data corroborate the theoretical analyses and illustrate the efficacy of the BFB solution in reducing the regression error, as compared to the non-boosted solution., Comment: 36 pages, 9 figures

Published
2022
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4. Fast Algorithms for Monotone Lower Subsets of Kronecker Least Squares Problems

Author

Malik, Osman Asif, Xu, Yiming, Cheng, Nuojin, Becker, Stephen, Doostan, Alireza, and Narayan, Akil

Subjects
Mathematics - Numerical Analysis, Computer Science - Data Structures and Algorithms
Abstract

Approximate solutions to large least squares problems can be computed efficiently using leverage score-based row-sketches, but directly computing the leverage scores, or sampling according to them with naive methods, still requires an expensive manipulation and processing of the design matrix. In this paper we develop efficient leverage score-based sampling methods for matrices with certain Kronecker product-type structure; in particular we consider matrices that are monotone lower column subsets of Kronecker product matrices. Our discussion is general, encompassing least squares problems on infinite domains, in which case matrices formally have infinitely many rows. We briefly survey leverage score-based sampling guarantees from the numerical linear algebra and approximation theory communities, and follow this with efficient algorithms for sampling when the design matrix has Kronecker-type structure. Our numerical examples confirm that sketches based on exact leverage score sampling for our class of structured matrices achieve superior residual compared to approximate leverage score sampling methods., Comment: 33 pages, 5 figures

Published
2022

6. FIGURE 5 from Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion

Author

Kim, Jong Hyuk, primary, Schulte, Ashley J., primary, Sarver, Aaron L., primary, Lee, Donghee, primary, Angelos, Mathew G., primary, Frantz, Aric M., primary, Forster, Colleen L., primary, O'Brien, Timothy D., primary, Cornax, Ingrid, primary, O'Sullivan, M. Gerard, primary, Cheng, Nuojin, primary, Lewellen, Mitzi, primary, Oseth, LeAnn, primary, Kumar, Sunil, primary, Bullman, Susan, primary, Pedamallu, Chandra Sekhar, primary, Goyal, Sagar M., primary, Meyerson, Matthew, primary, Lund, Troy C., primary, Breen, Matthew, primary, Lindblad-Toh, Kerstin, primary, Dickerson, Erin B., primary, Kaufman, Dan S., primary, and Modiano, Jaime F., primary

Published
2024
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7. FIGURE 2 from Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion

Author

Kim, Jong Hyuk, primary, Schulte, Ashley J., primary, Sarver, Aaron L., primary, Lee, Donghee, primary, Angelos, Mathew G., primary, Frantz, Aric M., primary, Forster, Colleen L., primary, O'Brien, Timothy D., primary, Cornax, Ingrid, primary, O'Sullivan, M. Gerard, primary, Cheng, Nuojin, primary, Lewellen, Mitzi, primary, Oseth, LeAnn, primary, Kumar, Sunil, primary, Bullman, Susan, primary, Pedamallu, Chandra Sekhar, primary, Goyal, Sagar M., primary, Meyerson, Matthew, primary, Lund, Troy C., primary, Breen, Matthew, primary, Lindblad-Toh, Kerstin, primary, Dickerson, Erin B., primary, Kaufman, Dan S., primary, and Modiano, Jaime F., primary

Published
2024
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8. Supplementary Figure S2 from Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion

Author

Kim, Jong Hyuk, primary, Schulte, Ashley J., primary, Sarver, Aaron L., primary, Lee, Donghee, primary, Angelos, Mathew G., primary, Frantz, Aric M., primary, Forster, Colleen L., primary, O'Brien, Timothy D., primary, Cornax, Ingrid, primary, O'Sullivan, M. Gerard, primary, Cheng, Nuojin, primary, Lewellen, Mitzi, primary, Oseth, LeAnn, primary, Kumar, Sunil, primary, Bullman, Susan, primary, Pedamallu, Chandra Sekhar, primary, Goyal, Sagar M., primary, Meyerson, Matthew, primary, Lund, Troy C., primary, Breen, Matthew, primary, Lindblad-Toh, Kerstin, primary, Dickerson, Erin B., primary, Kaufman, Dan S., primary, and Modiano, Jaime F., primary

Published
2024
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9. FIGURE 3 from Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion

Author

Kim, Jong Hyuk, primary, Schulte, Ashley J., primary, Sarver, Aaron L., primary, Lee, Donghee, primary, Angelos, Mathew G., primary, Frantz, Aric M., primary, Forster, Colleen L., primary, O'Brien, Timothy D., primary, Cornax, Ingrid, primary, O'Sullivan, M. Gerard, primary, Cheng, Nuojin, primary, Lewellen, Mitzi, primary, Oseth, LeAnn, primary, Kumar, Sunil, primary, Bullman, Susan, primary, Pedamallu, Chandra Sekhar, primary, Goyal, Sagar M., primary, Meyerson, Matthew, primary, Lund, Troy C., primary, Breen, Matthew, primary, Lindblad-Toh, Kerstin, primary, Dickerson, Erin B., primary, Kaufman, Dan S., primary, and Modiano, Jaime F., primary

Published
2024
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10. Supplementary Table S5 from Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion

Author

Kim, Jong Hyuk, primary, Schulte, Ashley J., primary, Sarver, Aaron L., primary, Lee, Donghee, primary, Angelos, Mathew G., primary, Frantz, Aric M., primary, Forster, Colleen L., primary, O'Brien, Timothy D., primary, Cornax, Ingrid, primary, O'Sullivan, M. Gerard, primary, Cheng, Nuojin, primary, Lewellen, Mitzi, primary, Oseth, LeAnn, primary, Kumar, Sunil, primary, Bullman, Susan, primary, Pedamallu, Chandra Sekhar, primary, Goyal, Sagar M., primary, Meyerson, Matthew, primary, Lund, Troy C., primary, Breen, Matthew, primary, Lindblad-Toh, Kerstin, primary, Dickerson, Erin B., primary, Kaufman, Dan S., primary, and Modiano, Jaime F., primary

Published
2024
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11. FIGURE 4 from Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion

Author

Kim, Jong Hyuk, primary, Schulte, Ashley J., primary, Sarver, Aaron L., primary, Lee, Donghee, primary, Angelos, Mathew G., primary, Frantz, Aric M., primary, Forster, Colleen L., primary, O'Brien, Timothy D., primary, Cornax, Ingrid, primary, O'Sullivan, M. Gerard, primary, Cheng, Nuojin, primary, Lewellen, Mitzi, primary, Oseth, LeAnn, primary, Kumar, Sunil, primary, Bullman, Susan, primary, Pedamallu, Chandra Sekhar, primary, Goyal, Sagar M., primary, Meyerson, Matthew, primary, Lund, Troy C., primary, Breen, Matthew, primary, Lindblad-Toh, Kerstin, primary, Dickerson, Erin B., primary, Kaufman, Dan S., primary, and Modiano, Jaime F., primary

Published
2024
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12. FIGURE 1 from Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion

Author

Kim, Jong Hyuk, primary, Schulte, Ashley J., primary, Sarver, Aaron L., primary, Lee, Donghee, primary, Angelos, Mathew G., primary, Frantz, Aric M., primary, Forster, Colleen L., primary, O'Brien, Timothy D., primary, Cornax, Ingrid, primary, O'Sullivan, M. Gerard, primary, Cheng, Nuojin, primary, Lewellen, Mitzi, primary, Oseth, LeAnn, primary, Kumar, Sunil, primary, Bullman, Susan, primary, Pedamallu, Chandra Sekhar, primary, Goyal, Sagar M., primary, Meyerson, Matthew, primary, Lund, Troy C., primary, Breen, Matthew, primary, Lindblad-Toh, Kerstin, primary, Dickerson, Erin B., primary, Kaufman, Dan S., primary, and Modiano, Jaime F., primary

Published
2024
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13. Data from Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion

Author

Kim, Jong Hyuk, primary, Schulte, Ashley J., primary, Sarver, Aaron L., primary, Lee, Donghee, primary, Angelos, Mathew G., primary, Frantz, Aric M., primary, Forster, Colleen L., primary, O'Brien, Timothy D., primary, Cornax, Ingrid, primary, O'Sullivan, M. Gerard, primary, Cheng, Nuojin, primary, Lewellen, Mitzi, primary, Oseth, LeAnn, primary, Kumar, Sunil, primary, Bullman, Susan, primary, Pedamallu, Chandra Sekhar, primary, Goyal, Sagar M., primary, Meyerson, Matthew, primary, Lund, Troy C., primary, Breen, Matthew, primary, Lindblad-Toh, Kerstin, primary, Dickerson, Erin B., primary, Kaufman, Dan S., primary, and Modiano, Jaime F., primary

Published
2024
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14. Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion

Author

Kim, Jong Hyuk, Schulte, Ashley J., Sarver, Aaron L., Lee, Donghee, Angelos, Mathew G., Frantz, Aric M., Forster, Colleen L., O'Brien, Timothy D., Cornax, Ingrid, O'Sullivan, M. Gerard, Cheng, Nuojin, Lewellen, Mitzi, Oseth, LeAnn, Kumar, Sunil, Bullman, Susan, Pedamallu, Chandra Sekhar, Goyal, Sagar M., Meyerson, Matthew, Lund, Troy C., Breen, Matthew, Lindblad-Toh, Kerstin, Dickerson, Erin B., Kaufman, Dan S., Modiano, Jaime F., Kim, Jong Hyuk, Schulte, Ashley J., Sarver, Aaron L., Lee, Donghee, Angelos, Mathew G., Frantz, Aric M., Forster, Colleen L., O'Brien, Timothy D., Cornax, Ingrid, O'Sullivan, M. Gerard, Cheng, Nuojin, Lewellen, Mitzi, Oseth, LeAnn, Kumar, Sunil, Bullman, Susan, Pedamallu, Chandra Sekhar, Goyal, Sagar M., Meyerson, Matthew, Lund, Troy C., Breen, Matthew, Lindblad-Toh, Kerstin, Dickerson, Erin B., Kaufman, Dan S., and Modiano, Jaime F.

Abstract

Hemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs which support the niche that enables progression of canine hemangiosarcoma and human angiosarcoma. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells. In a series of xenografts, we observed that the transplanted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. Our functional analyses indicate that hemangiosarcoma cells generate a microenvironment that supports expansion and differentiation of hematopoietic progenitor populations. Furthermore, gene expression profiling data revealed hemangiosarcoma cells expressed a repertoire of hematopoietic cytokines capable of regulating the surrounding stromal cells. We conclude that canine hemangiosarcomas, and possibly human angiosarcomas, maintain molecular properties that provide hematopoietic support and facilitate stromal reactions, suggesting their potential involvement in promoting the growth of hematopoietic tumors.Significance: We demonstrate that hemangiosarcomas regulate molecular programs supporting hematopoietic expansion and differentiation, providing insights into their potential roles in creating a permissive stromal-immune environment for tumor progression.

Published
2024
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16. Protective role of agarwood essential oil and compounds thereof in crop‐associated fungal pathogens.

Author

Liu, Jing, Cheng, Nuojin, Li, Yuan, Jiang, Xingtao, Luo, Qi, and Wu, Zehong

Subjects
*ESSENTIAL oils, *CARVACROL, *FOOD pathogens, *AGRICULTURAL development, *AGRICULTURE, *ANTIFUNGAL agents
Abstract

The potential risk of fungal pathogen infection in agriculture has great adverse effects on agricultural development and human health. In this study, we explored the application of agarwood essential oil (AEO) and its main components in the development of agricultural fungicides. The compositions of AEO produced in Maoming City of Guangdong Province, China was firstly analysed by GC–MS. AEO and compounds thereof including carvacrol and longifolene were then used to perform a series of antifungal activity evaluations in vitro and in vivo against agricultural and foodborne pathogens. The in vitro results showed that the antifungal activities of AEO were comparable to those of hymexazol (a positive control), and carvacrol exhibited stronger efficacy. In vivo studies also showed that AEO and carvacrol could significantly inhibit the damage effect of Curvularia mebaldsii on the germination rate of wheat roots. Further, it was found that the germination rate exhibited a downward trend with the dose increase of AEO and carvacrol. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Data from Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions

Author

Kim, Jong Hyuk, primary, Megquier, Kate, primary, Thomas, Rachael, primary, Sarver, Aaron L., primary, Song, Jung Min, primary, Kim, Yoon Tae, primary, Cheng, Nuojin, primary, Schulte, Ashley J., primary, Linden, Michael A., primary, Murugan, Paari, primary, Oseth, LeAnn, primary, Forster, Colleen L., primary, Elvers, Ingegerd, primary, Swofford, Ross, primary, Turner-Maier, Jason, primary, Karlsson, Elinor K., primary, Breen, Matthew, primary, Lindblad-Toh, Kerstin, primary, and Modiano, Jaime F., primary

Published
2023
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18. Supplementary Tables 1-15 from Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions

Author

Kim, Jong Hyuk, primary, Megquier, Kate, primary, Thomas, Rachael, primary, Sarver, Aaron L., primary, Song, Jung Min, primary, Kim, Yoon Tae, primary, Cheng, Nuojin, primary, Schulte, Ashley J., primary, Linden, Michael A., primary, Murugan, Paari, primary, Oseth, LeAnn, primary, Forster, Colleen L., primary, Elvers, Ingegerd, primary, Swofford, Ross, primary, Turner-Maier, Jason, primary, Karlsson, Elinor K., primary, Breen, Matthew, primary, Lindblad-Toh, Kerstin, primary, and Modiano, Jaime F., primary

Published
2023
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19. Supplementary Figures 1-12 from Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions

Author

Kim, Jong Hyuk, primary, Megquier, Kate, primary, Thomas, Rachael, primary, Sarver, Aaron L., primary, Song, Jung Min, primary, Kim, Yoon Tae, primary, Cheng, Nuojin, primary, Schulte, Ashley J., primary, Linden, Michael A., primary, Murugan, Paari, primary, Oseth, LeAnn, primary, Forster, Colleen L., primary, Elvers, Ingegerd, primary, Swofford, Ross, primary, Turner-Maier, Jason, primary, Karlsson, Elinor K., primary, Breen, Matthew, primary, Lindblad-Toh, Kerstin, primary, and Modiano, Jaime F., primary

Published
2023
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20. Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions

Author

Kim, Jong Hyuk, Megquier, Kate, Thomas, Rachael, Sarver, Aaron L., Song, Jung Min, Kim, Yoon Tae, Cheng, Nuojin, Schulte, Ashley J., Linden, Michael A., Murugan, Paari, Oseth, LeAnn, Forster, Colleen L., Elvers, Ingegerd, Swofford, Ross, Turner-Maier, Jason, Karlsson, Elinor K., Breen, Matthew, Lindblad-Toh, Kerstin, Modiano, Jaime F., Kim, Jong Hyuk, Megquier, Kate, Thomas, Rachael, Sarver, Aaron L., Song, Jung Min, Kim, Yoon Tae, Cheng, Nuojin, Schulte, Ashley J., Linden, Michael A., Murugan, Paari, Oseth, LeAnn, Forster, Colleen L., Elvers, Ingegerd, Swofford, Ross, Turner-Maier, Jason, Karlsson, Elinor K., Breen, Matthew, Lindblad-Toh, Kerstin, and Modiano, Jaime F.

Abstract

Sporadic angiosarcomas are aggressive vascular sarcomas whose rarity and genomic complexity present significant obstacles in deciphering the pathogenic significance of individual genetic alterations. Numerous fusion genes have been identified across multiple types of cancers, but their existence and significance remain unclear in sporadic angiosarcomas. In this study, we leveraged RNA-sequencing data from 13 human angiosarcomas and 76 spontaneous canine hemangiosarcomas to identify fusion genes associated with spontaneous vascular malignancies. Ten novel protein-coding fusion genes, including TEX2-PECAM1 and ATP8A2-FLT1, were identified in seven of the 13 human tumors, with two tumors showing mutations of TP53. HRAS and NRAS mutations were found in angiosarcomas without fusions or TP53 mutations. We found 15 novel protein-coding fusion genes including MYO16-PTK2, GABRA3-FLT1, and AKT3-XPNPEP1 in 11 of the 76 canine hemangiosarcomas; these fusion genes were seen exclusively in tumors of the angiogenic molecular subtype that contained recurrent mutations in TP53, PIK3CA, PIK3R1, and NRAS. In particular, fusion genes and mutations of TP53 cooccurred in tumors with higher frequency than expected by random chance, and they enriched gene signatures predicting activation of angiogenic pathways. Comparative transcriptomic analysis of human angiosarcomas and canine hemangiosarcomas identified shared molecular signatures associated with activation of PI3K/AKT/mTOR pathways. Our data suggest that genome instability induced by TP53 mutations might create a predisposition for fusion events that may contribute to tumor progression by promoting selection and/or enhancing fitness through activation of convergent angiogenic pathways in this vascular malignancy. Implications: This study shows that, while drive events of malignant vasoformative tumors of humans and dogs include diverse mutations and stochastic rearrangements that create novel fusion genes, convergent transcriptional p

Published
2021
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21. Hemangiosarcoma Cells Promote Conserved Host-Derived Hematopoietic Expansion

Author

Kim, Jong Hyuk, primary, Schulte, Ashley J., additional, Sarver, Aaron L., additional, Angelos, Mathew G., additional, Frantz, Aric M., additional, Forster, Colleen L., additional, O’Brien, Timothy D., additional, Cornax, Ingrid, additional, O’Sullivan, M. Gerard, additional, Cheng, Nuojin, additional, Lewellen, Mitzi, additional, Oseth, LeAnn, additional, Kumar, Sunil, additional, Bullman, Susan, additional, Pedamallu, Chandra Sekhar, additional, Goyal, Sagar M., additional, Meyerson, Matthew, additional, Lund, Troy C., additional, Alfoldi, Jessica, additional, Breen, Matthew, additional, Lindblad-Toh, Kerstin, additional, Dickerson, Erin B., additional, Kaufman, Dan S., additional, and Modiano, Jaime F., additional

Published
2021
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22. Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions

Author

Kim, Jong Hyuk, primary, Megquier, Kate, additional, Thomas, Rachael, additional, Sarver, Aaron L., additional, Song, Jung Min, additional, Kim, Yoon Tae, additional, Cheng, Nuojin, additional, Schulte, Ashley J., additional, Linden, Michael A., additional, Murugan, Paari, additional, Oseth, LeAnn, additional, Forster, Colleen L., additional, Elvers, Ingegerd, additional, Swofford, Ross, additional, Turner-Maier, Jason, additional, Karlsson, Elinor K., additional, Breen, Matthew, additional, Lindblad-Toh, Kerstin, additional, and Modiano, Jaime F., additional

Published
2021
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24. Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions

Author

Kim, Jong Hyuk, primary, Megquier, Kate, additional, Thomas, Rachael, additional, Sarver, Aaron L., additional, Song, Jung Min, additional, Kim, Yoon Tae, additional, Cheng, Nuojin, additional, Schulte, Ashley J., additional, Linden, Michael A., additional, Murugan, Paari, additional, Oseth, LeAnn, additional, Forster, Colleen L., additional, Elvers, Ingegerd, additional, Swofford, Ross, additional, Turner-Maier, Jason, additional, Karlsson, Elinor K., additional, Breen, Matthew, additional, Lindblad-Toh, Kerstin, additional, and Modiano, Jaime F., additional

Published
2020
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25. Machine learning application identifies novel gene signatures from transcriptomic data of spontaneous canine hemangiosarcoma.

Author

Cheng, Nuojin, Schulte, Ashley J, Santosa, Fadil, and Kim, Jong Hyuk

Subjects
*MACHINE learning, *ANGIOSARCOMA, *TRANSCRIPTOMES, *NUCLEOTIDE sequencing, *DOGS, *FEATURE selection
Abstract

Angiosarcomas are soft-tissue sarcomas that form malignant vascular tissues. Angiosarcomas are very rare, and due to their aggressive behavior and high metastatic propensity, they have poor clinical outcomes. Hemangiosarcomas commonly occur in domestic dogs, and share pathological and clinical features with human angiosarcomas. Typical pathognomonic features of this tumor are irregular vascular channels that are filled with blood and are lined by a mixture of malignant and nonmalignant endothelial cells. The current gold standard is the histological diagnosis of angiosarcoma; however, microscopic evaluation may be complicated, particularly when tumor cells are undetectable due to the presence of excessive amounts of nontumor cells or when tissue specimens have insufficient tumor content. In this study, we implemented machine learning applications from next-generation transcriptomic data of canine hemangiosarcoma tumor samples (n  = 76) and nonmalignant tissues (n  = 10) to evaluate their training performance for diagnostic utility. The 10-fold cross-validation test and multiple feature selection methods were applied. We found that extra trees and random forest learning models were the best classifiers for hemangiosarcoma in our testing datasets. We also identified novel gene signatures using the mutual information and Monte Carlo feature selection method. The extra trees model revealed high classification accuracy for hemangiosarcoma in validation sets. We demonstrate that high-throughput sequencing data of canine hemangiosarcoma are trainable for machine learning applications. Furthermore, our approach enables us to identify novel gene signatures as reliable determinants of hemangiosarcoma, providing significant insights into the development of potential applications for this vascular malignancy. [ABSTRACT FROM AUTHOR]

Published
2021
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26. Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion.

Author

Kim JH, Schulte AJ, Sarver AL, Lee D, Angelos MG, Frantz AM, Forster CL, O'Brien TD, Cornax I, O'Sullivan MG, Cheng N, Lewellen M, Oseth L, Kumar S, Bullman S, Pedamallu CS, Goyal SM, Meyerson M, Lund TC, Breen M, Lindblad-Toh K, Dickerson EB, Kaufman DS, and Modiano JF

Subjects
Dogs, Animals, Humans, Mice, Tumor Microenvironment, Hematopoietic Stem Cells pathology, Hematopoiesis, Cell Differentiation, Hemangiosarcoma pathology, Hemangiosarcoma veterinary, Hemangiosarcoma genetics
Abstract

Hemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs which support the niche that enables progression of canine hemangiosarcoma and human angiosarcoma. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells. In a series of xenografts, we observed that the transplanted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. Our functional analyses indicate that hemangiosarcoma cells generate a microenvironment that supports expansion and differentiation of hematopoietic progenitor populations. Furthermore, gene expression profiling data revealed hemangiosarcoma cells expressed a repertoire of hematopoietic cytokines capable of regulating the surrounding stromal cells. We conclude that canine hemangiosarcomas, and possibly human angiosarcomas, maintain molecular properties that provide hematopoietic support and facilitate stromal reactions, suggesting their potential involvement in promoting the growth of hematopoietic tumors., Significance: We demonstrate that hemangiosarcomas regulate molecular programs supporting hematopoietic expansion and differentiation, providing insights into their potential roles in creating a permissive stromal-immune environment for tumor progression., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Published
2024
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