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19 results on '"Cai, Cathy"'

1. A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling

Author

Hackney, Jason A, Shivram, Haridha, Vander Heiden, Jason, Overall, Chris, Orozco, Luz, Gao, Xia, Kim, Eugene, West, Nathan, Qamra, Aditi, Chang, Diana, Chakrabarti, Arindam, Choy, David F, Combes, Alexis J, Courau, Tristan, Fragiadakis, Gabriela K, Rao, Arjun Arkal, Ray, Arja, Tsui, Jessica, Hu, Kenneth, Kuhn, Nicholas F, Krummel, Matthew F, Erle, David J, Kangelaris, Kirsten, Sarma, Aartik, Lyon, Zoe, Calfee, Carolyn S, Woodruff, Prescott G, Ghale, Rajani, Mick, Eran, Byrne, Ashley, Zha, Beth Shoshana, Langelier, Charles, Hendrickson, Carolyn M, van der Wijst, Monique GP, Hartoularos, George C, Grant, Tianna, Bueno, Raymund, Lee, David S, Greenland, John R, Sun, Yang, Perez, Richard, Ogorodnikov, Anton, Ward, Alyssa, Ye, Chun Jimmie, Consortium, UCSF COMET, Abe-Jones, Yumiko, Adkisson, Michael, Ansel, K Mark, Asthana, Saurabh, Beagle, Alexander, Bhide, Sharvari, Cai, Cathy, Caldera, Saharai, Calvo, Maria, Carrillo, Sidney A, Chak, Suzanna, Christenson, Stephanie, Collins, Zachary, Darmanis, Spyros, Detweiler, Angela, DeVoe, Catherine, Eckalbar, Walter, Giberson, Jeremy, Gonzalez, Ana, Gordon, Gracie, Serpa, Paula Hayakawa, Jauregui, Alejandra, Jones, Chayse, Ke, Serena, Kushnoor, Divya, Lea, Tasha, Lee, Deanna, Leligdowicz, Aleksandra, Liu, Yale, Mahboob, Salman, Maliskova, Lenka, Matthay, Michael, McCarthy, Elizabeth, Muñoz-Sandoval, Priscila, Neff, Norma, Nguyen, Viet, Nigam, Nishita, Parada, Randy, Phelps, Maira, Pierce, Logan, Prasad, Priya, Rashid, Sadeed, Reeder, Gabriella, Rodriguez, Nicklaus, Samad, Bushra, Schroeder, Andrew, Shaw, Cole, Shen, Alan, Sigman, Austin, Sinha, Pratik, Spitzer, Matthew, Sunshine, Sara, Tang, Kevin, Altamirano, Luz Torres, and Tsitsiklis, Alexandra

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Rare Diseases, Emerging Infectious Diseases, Lung, Infectious Diseases, Clinical Research, Acute Respiratory Distress Syndrome, Coronaviruses, 2.1 Biological and endogenous factors, Good Health and Well Being, UCSF COMET Consortium, Clinical genetics, Immune response, Molecular medicine
Abstract

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. IL-6 signaling blockade by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of EN-RAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

Published
2023

2. Mass cytometry reveals a conserved immune trajectory of recovery in hospitalized COVID-19 patients

Author

Burnett, Cassandra E, Okholm, Trine Line Hauge, Tenvooren, Iliana, Marquez, Diana M, Tamaki, Stanley, Sandoval, Priscila Munoz, Willmore, Andrew, Consortium, The UCSF COMET, Patel, Ravi, Abe-Jones, Yumiko, Asthana, Saurabh, Beagle, Alexander, Bhide, Sharvari, Cai, Cathy, Calvo, Maria, Carrillo, Sidney A, Chak, Suzanna, Collins, Zachary, Darmanis, Spyros, Fragiadakis, Gabriela K, Ghale, Rajani, Giberson, Jeremy, Glenn, Pat, Gonzalez, Ana, Hiam-Galvez, Kamir, Jauregui, Alejandra, Ke, Serena, Lea, Tasha, Lee, Deanna, Lota, Raphael, Lupin-Jimenez, Leonard, Nguyen, Viet, Nigam, Nishita, Pierce, Logan, Prasad, Priya, Rao, Arjun, Rashid, Sadeed, Rodriguez, Nicklaus, Samad, Bushra, Shaw, Cole, Sigman, Austin, Sinha, Pratik, Tang, Kevin, Altamirano, Luz Torres, Tumurbaatar, Erden, Upadhyay, Vaibhav, Ward, Alyssa, Wong, Kristine, Ye, Chun Jimmie, Yee, Kimberly, Zhou, Mingyue, Hendrickson, Carolyn M, Kangelaris, Kirsten N, Langelier, Charles R, Krummel, Matthew F, Woodruff, Prescott G, Calfee, Carolyn S, Erle, David J, Ansel, K Mark, and Spitzer, Matthew H

Subjects
Biomedical and Clinical Sciences, Immunology, Pneumonia & Influenza, Pneumonia, Clinical Research, Lung, Infectious Diseases, Hematology, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Good Health and Well Being, COVID-19, Disease Progression, Humans, SARS-CoV-2, UCSF COMET Consortium, disease resolution, immune cell signaling, immune response, recovery
Abstract

While studies have elucidated many pathophysiological elements of COVID-19, little is known about immunological changes during COVID-19 resolution. We analyzed immune cells and phosphorylated signaling states at single-cell resolution from longitudinal blood samples of patients hospitalized with COVID-19, pneumonia and/or sepsis, and healthy individuals by mass cytometry. COVID-19 patients showed distinct immune compositions and an early, coordinated, and elevated immune cell signaling profile associated with early hospital discharge. Intra-patient longitudinal analysis revealed changes in myeloid and T cell frequencies and a reduction in immune cell signaling across cell types that accompanied disease resolution and discharge. These changes, together with increases in regulatory T cells and reduced signaling in basophils, also accompanied recovery from respiratory failure and were associated with better outcomes at time of admission. Therefore, although patients have heterogeneous immunological baselines and highly variable disease courses, a core immunological trajectory exists that defines recovery from severe SARS-CoV-2 infection.

Published
2022

3. Discovering dominant tumor immune archetypes in a pan-cancer census

Author

Combes, Alexis J, Samad, Bushra, Tsui, Jessica, Chew, Nayvin W, Yan, Peter, Reeder, Gabriella C, Kushnoor, Divyashree, Shen, Alan, Davidson, Brittany, Barczak, Andrea J, Adkisson, Michael, Edwards, Austin, Naser, Mohammad, Barry, Kevin C, Courau, Tristan, Hammoudi, Taymour, Argüello, Rafael J, Rao, Arjun Arkal, Olshen, Adam B, Consortium, The Immunoprofiler, Spitzer, Matthew, Fong, Lawrence, Nelson, Amanda, Kumar, Raj, Lee, Justin, Burra, Arun, Hsu, Joy, Hackett, Caroline, Tolentino, Karen, Sjarif, Jasmine, Johnson, Peter, Shao, Evans, Abrau, Darrell, Lupin, Leonard, Shaw, Cole, Collins, Zachary, Lea, Tasha, Corvera, Carlos, Nakakura, Eric, Carnevale, Julia, Alvarado, Michael, Loo, Kimberley, Chen, Lawrence, Chow, Melissa, Grandis, Jennifer, Ryan, Will, El-Sayed, Ivan, Jablons, David, Woodard, Gavitt, Meng, Maxwell W, Porten, Sima P, Okada, Hideho, Tempero, Margaret, Ko, Andrew, Kirkwood, Kim, Vandenberg, Scott, Guevarra, Denise, Oropeza, Erica, Cyr, Chris, Glenn, Pat, Bolen, Jennifer, Morton, Amanda, Eckalbar, Walter, Cai, Cathy, Zhan, Jenny, Davis, Katelyn C, Kelley, Robin K, Chapman, Jocelyn S, Atreya, Chloe E, Patel, Amar, Daud, Adil I, Ha, Patrick, Diaz, Aaron A, Kratz, Johannes R, Collisson, Eric A, Fragiadakis, Gabriela K, Erle, David J, Boissonnas, Alexandre, Asthana, Saurabh, Chan, Vincent, and Krummel, Matthew F

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer Genomics, Cancer, Genetics, Human Genome, Biomarkers, Tumor, Censuses, Cluster Analysis, Cohort Studies, Computational Biology, Flow Cytometry, Gene Expression Regulation, Neoplastic, Humans, Neoplasms, RNA-Seq, San Francisco, Transcriptome, Tumor Microenvironment, Universities, Immunoprofiler Consortium, Pan Cancer analysis, immune profiling, solid tumor microenvironement, system immunology, tumor immunology, unsupervised clustering, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations, and other features of the surrounding tissue. It is likely that individual tumors engage common patterns of the immune system-here "archetypes"-creating prototypical non-destructive tumor immune microenvironments (TMEs) and modulating tumor-targeting. To discover the dominant immune system archetypes, the University of California, San Francisco (UCSF) Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub-compartments uncovered dominant patterns of immune composition across cancers. These archetypes were profound insofar as they also differentiated tumors based upon unique immune and tumor gene-expression patterns. They also partitioned well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune organization and provides a rational path forward to learn how to modulate these to improve therapy.

Published
2022

4. Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19

Author

van der Wijst, Monique GP, Vazquez, Sara E, Hartoularos, George C, Bastard, Paul, Grant, Tianna, Bueno, Raymund, Lee, David S, Greenland, John R, Sun, Yang, Perez, Richard, Ogorodnikov, Anton, Ward, Alyssa, Mann, Sabrina A, Lynch, Kara L, Yun, Cassandra, Havlir, Diane V, Chamie, Gabriel, Marquez, Carina, Greenhouse, Bryan, Lionakis, Michail S, Norris, Philip J, Dumont, Larry J, Kelly, Kathleen, Zhang, Peng, Zhang, Qian, Gervais, Adrian, Le Voyer, Tom, Whatley, Alexander, Si, Yichen, Byrne, Ashley, Combes, Alexis J, Rao, Arjun Arkal, Song, Yun S, Fragiadakis, Gabriela K, Kangelaris, Kirsten, Calfee, Carolyn S, Erle, David J, Hendrickson, Carolyn, Krummel, Matthew F, Woodruff, Prescott G, Langelier, Charles R, Casanova, Jean-Laurent, Derisi, Joseph L, Anderson, Mark S, Ye, Chun Jimmie, consortium, on behalf of the UCSF COMET, Abe-Jones, Yumiko, Alvarenga, Bonny, Asthana, Saurabh, Beagle, Alexander, Bhakta, Tanvi, Bhide, Sharvari, Cai, Cathy, Calvo, Maria, Carrillo, Sidney A, Chak, Suzanna, Collins, Zachary, Dandekar, Ravi, Darmanis, Spyros, Esmaili, Armond, Ghale, Rajani, Giberson, Jeremy, Glenn, Pat, Gonzalez, Ana, Jauregui, Alejandra, Jones, Norman, Ke, Serena, Lea, Tasha, Lee, Deanna, Lelidowicz, Aleskandra, Liu, Kathleen, Lota, Raphael, Matthay, Michael, Milush, Jeff, Nguyen, Viet, Nigam, Nishita, Ortiz, Gabe, Pierce, Logan, Prasad, Priya, Rajan, Jayant, Rashid, Ahmad Sadeed, Rodriguez, Nicklaus, Samad, Bushra, Scarlet, Diane, Shaw, Cole, Sigman, Austin, Sinha, Pratik, Spitzer, Matthew, Tang, Kevin, Altamirano, Luz Torres, Tumurbaatar, Erden, Willmore, Andrew, Wilson, Michael, Withers, Reese, Yee, Kimberly, Zamecnik, Colin, Zhan, Jenny, and Zhou, Mingyue

Subjects
Biomedical and Clinical Sciences, Immunology, Coronaviruses, Clinical Research, Emerging Infectious Diseases, Genetics, Infectious Diseases, Lung, 2.1 Biological and endogenous factors, Inflammatory and immune system, Good Health and Well Being, Autoantibodies, COVID-19, Humans, Interferon Type I, UCSF COMET consortium, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN–specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non–COVID-19 controls revealed a lack of type I IFN–stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN–specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN–specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms.

Published
2021

5. A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling

Author

Abe-Jones, Yumiko, Adkisson, Michael, Ansel, K. Mark, Asthana, Saurabh, Beagle, Alexander, Bhide, Sharvari, Cai, Cathy, Caldera, Saharai, Calvo, Maria, Carrillo, Sidney A., Chak, Suzanna, Christenson, Stephanie, Collins, Zachary, Darmanis, Spyros, Detweiler, Angela, DeVoe, Catherine, Eckalbar, Walter, Giberson, Jeremy, Gonzalez, Ana, Gordon, Gracie, Serpa, Paula Hayakawa, Jauregui, Alejandra, Jones, Chayse, Ke, Serena, Kushnoor, Divya, Lea, Tasha, Lee, Deanna, Leligdowicz, Aleksandra, Liu, Yale, Mahboob, Salman, Maliskova, Lenka, Matthay, Michael, McCarthy, Elizabeth, Muñoz-Sandoval, Priscila, Neff, Norma, Nguyen, Viet, Nigam, Nishita, Parada, Randy, Phelps, Maira, Pierce, Logan, Prasad, Priya, Rashid, Sadeed, Reeder, Gabriella, Rodriguez, Nicklaus, Samad, Bushra, Schroeder, Andrew, Shaw, Cole, Shen, Alan, Sigman, Austin, Sinha, Pratik, Spitzer, Matthew, Sunshine, Sara, Tang, Kevin, Altamirano, Luz Torres, Tsitsiklis, Alexandra, Tumurbaatar, Erden, Upadhyay, Vaibhav, Whatley, Alexander, Willmore, Andrew, Wilson, Michael, Winkler, Juliane, Wong, Kristine, Yee, Kimberly, Yu, Michelle, Zhou, Mingyue, Zhu, Wandi S., Hackney, Jason A., Shivram, Haridha, Vander Heiden, Jason, Overall, Chris, Orozco, Luz, Gao, Xia, Kim, Eugene, West, Nathan, Qamra, Aditi, Chang, Diana, Chakrabarti, Arindam, Choy, David F., Combes, Alexis J., Courau, Tristan, Fragiadakis, Gabriela K., Rao, Arjun Arkal, Ray, Arja, Tsui, Jessica, Hu, Kenneth, Kuhn, Nicholas F., Krummel, Matthew F., Erle, David J., Kangelaris, Kirsten, Sarma, Aartik, Lyon, Zoe, Calfee, Carolyn S., Woodruff, Prescott G., Ghale, Rajani, Mick, Eran, Byrne, Ashley, Zha, Beth Shoshana, Langelier, Charles, Hendrickson, Carolyn M., van der Wijst, Monique G.P., Hartoularos, George C., Grant, Tianna, Bueno, Raymund, Lee, David S., Greenland, John R., Sun, Yang, Perez, Richard, Ogorodnikov, Anton, Ward, Alyssa, Ye, Chun Jimmie, Ramalingam, Thiru, McBride, Jacqueline M., Cai, Fang, Teterina, Anastasia, Bao, Min, Tsai, Larry, Rosas, Ivan O., Regev, Aviv, Kapadia, Sharookh B., Bauer, Rebecca N., and Rosenberger, Carrie M.

Published
2023
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6. Mass cytometry reveals a conserved immune trajectory of recovery in hospitalized COVID-19 patients

Author

Patel, Ravi, Abe-Jones, Yumiko, Asthana, Saurabh, Beagle, Alexander, Bhide, Sharvari, Cai, Cathy, Calvo, Maria, Carrillo, Sidney A., Chak, Suzanna, Collins, Zachary, Darmanis, Spyros, Fragiadakis, Gabriela K., Ghale, Rajani, Giberson, Jeremy, Glenn, Pat, Gonzalez, Ana, Hiam-Galvez, Kamir, Jauregui, Alejandra, Ke, Serena, Lea, Tasha, Lee, Deanna, Lota, Raphael, Lupin-Jimenez, Leonard, Nguyen, Viet, Nigam, Nishita, Pierce, Logan, Prasad, Priya, Rao, Arjun, Rashid, Sadeed, Rodriguez, Nicklaus, Samad, Bushra, Shaw, Cole, Sigman, Austin, Sinha, Pratik, Tang, Kevin, Altamirano, Luz Torres, Tumurbaatar, Erden, Upadhyay, Vaibhav, Ward, Alyssa, Wong, Kristine, Ye, Chun Jimmie, Yee, Kimberly, Zhou, Mingyue, Burnett, Cassandra E., Okholm, Trine Line Hauge, Tenvooren, Iliana, Marquez, Diana M., Tamaki, Stanley, Munoz Sandoval, Priscila, Willmore, Andrew, Hendrickson, Carolyn M., Kangelaris, Kirsten N., Langelier, Charles R., Krummel, Matthew F., Woodruff, Prescott G., Calfee, Carolyn S., Erle, David J., Ansel, K. Mark, and Spitzer, Matthew H.

Published
2022
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7. Discovering dominant tumor immune archetypes in a pan-cancer census

Author

Spitzer, Matthew, Fong, Lawrence, Nelson, Amanda, Kumar, Raj, Lee, Justin, Burra, Arun, Hsu, Joy, Hackett, Caroline, Tolentino, Karen, Sjarif, Jasmine, Johnson, Peter, Shao, Evans, Abrau, Darrell, Lupin, Leonard, Shaw, Cole, Collins, Zachary, Lea, Tasha, Corvera, Carlos, Nakakura, Eric, Carnevale, Julia, Alvarado, Michael, Loo, Kimberley, Chen, Lawrence, Chow, Melissa, Grandis, Jennifer, Ryan, Will, El-Sayed, Ivan, Jablons, David, Woodard, Gavitt, Meng, Maxwell W., Porten, Sima P., Okada, Hideho, Tempero, Margaret, Ko, Andrew, Kirkwood, Kim, Vandenberg, Scott, Guevarra, Denise, Oropeza, Erica, Cyr, Chris, Glenn, Pat, Bolen, Jennifer, Morton, Amanda, Eckalbar, Walter, Combes, Alexis J., Samad, Bushra, Tsui, Jessica, Chew, Nayvin W., Yan, Peter, Reeder, Gabriella C., Kushnoor, Divyashree, Shen, Alan, Davidson, Brittany, Barczak, Andrea J., Adkisson, Michael, Edwards, Austin, Naser, Mohammad, Barry, Kevin C., Courau, Tristan, Hammoudi, Taymour, Argüello, Rafael J., Rao, Arjun Arkal, Olshen, Adam B., Cai, Cathy, Zhan, Jenny, Davis, Katelyn C., Kelley, Robin K., Chapman, Jocelyn S., Atreya, Chloe E., Patel, Amar, Daud, Adil I., Ha, Patrick, Diaz, Aaron A., Kratz, Johannes R., Collisson, Eric A., Fragiadakis, Gabriela K., Erle, David J., Boissonnas, Alexandre, Asthana, Saurabh, Chan, Vincent, and Krummel, Matthew F.

Published
2022
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10. The reaction of sponsor stock prices to clinical trial outcomes: An event study analysis

Author

Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Sloan School of Management. Laboratory for Financial Engineering, Sloan School of Management, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Singh, Manish, Rocafort, Roland, Cai, Cathy, Siah, Kien Wei, Lo, Andrew W, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Sloan School of Management. Laboratory for Financial Engineering, Sloan School of Management, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Singh, Manish, Rocafort, Roland, Cai, Cathy, Siah, Kien Wei, and Lo, Andrew W

Abstract

We perform an event study analysis that quantifies the market reaction to clinical trial result announcements for 13,807 trials from 2000 to 2020, one of the largest event studies of clinical trials to date. We first determine the specific dates in the clinical trial process on which the greatest impact on the stock prices of their sponsor companies occur. We then analyze the relationship between the abnormal returns observed on these dates due to the clinical trial outcome and the properties of the trial, such as its phase, target accrual, design category, and disease and sponsor company type (biotechnology or pharmaceutical). We find that the classification of a company as “early biotechnology” or “big pharmaceutical” had the most impact on abnormal returns, followed by properties such as disease, outcome, the phase of the clinical trial, and target accrual. We also find that these properties and classifications by themselves were insufficient to explain the variation in excess returns observed due to clinical trial outcomes.

Published
2022

11. Terrorism in China: the Muslim Uyghurs and the Han Chinese

Author

Cai, Cathy

Subjects
China National Petroleum Corp., Political parties -- China, Petroleum industry -- International economic relations, Communism -- China, Uighurs, Military and naval science, Communist Party of China, Shanghai Cooperation Organization
Abstract

Background For over five decades, the People's Republic of China has been implementing social, political, and economic programs aimed at placing the country on the global stage. Former Chairman of [...]

Published
2014

12. A Pan-Cancer Census of Dominant Tumor Immune Archetypes

Author

Combes, Alexis J., primary, Samad, Bushra, additional, Tsui, Jessica, additional, Chew, Nayvin W., additional, Yan, Peter, additional, Reeder, Gabriella C., additional, Kushnoor, Divyashree, additional, Shen, Alan, additional, Davidson, Brittany, additional, Barczak, Andrea J., additional, Adkisson, Michael, additional, Edwards, Austin, additional, Naser, Mohammad, additional, Barry, Kevin C., additional, Courau, Tristan, additional, Hammoudi, Taymour, additional, Arguello, Rafael, additional, Rao, Arjun Arkal, additional, Olshen, Adam B., additional, Consortium, The Immunoprofiler, additional, Cai, Cathy, additional, Zhan, Jenny, additional, Davis, Katelyn C., additional, Kelley, Robin K., additional, Chapman, Jocelyn S., additional, Attreya, Chloe E., additional, Patel, Amar, additional, Daud, Adlil, additional, Ha, Patrick, additional, Diaz, Aaron A., additional, Kratz, Johannes R., additional, Collisson, Eric A., additional, Fragiadakis, Gabriela K., additional, Erle, David J., additional, Boissonnas, Alexandre, additional, Asthana, Saurabh, additional, Chan, Vincent, additional, and Krummel, Matthew F., additional

Published
2021
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18. An integrated system for rapid process defect evaluation.

Author

Uritsky, Yuri and Cai, Cathy

Subjects
*SEMICONDUCTORS testing, *PROCESS control systems, *EQUIPMENT & supplies
Abstract

Describes the design of an semiconductor integrated analysis tool combining a laser particle scanner, a laser confocal microscope system and a SEM/EDX system. Laser confocal microscope operating principle; Applications of laser imaging; Ultrapointe volume imaging; Unclassifiable defects.

Published
1995

19. Synthetic Lethality Screening with Recursive Feature Machines.

Author

Cai C, Radhakrishnan A, and Uhler C

Abstract

Synthetic lethality refers to a genetic interaction where the simultaneous perturbation of gene pairs leads to cell death. Synthetically lethal gene pairs (SL pairs) provide a potential avenue for selectively targeting cancer cells based on genetic vulnerabilities. The rise of large-scale gene perturbation screens such as the Cancer Dependency Map (DepMap) offers the opportunity to identify SL pairs automatically using machine learning. We build on a recently developed class of feature learning kernel machines known as Recursive Feature Machines (RFMs) to develop a pipeline for identifying SL pairs based on CRISPR viability data from DepMap. In particular, we first train RFMs to predict viability scores for a given CRISPR gene knockout from cell line embeddings consisting of gene expression and mutation features. After training, RFMs use a statistical operator known as average gradient outer product to provide weights for each feature indicating the importance of each feature in predicting cellular viability. We subsequently apply correlation-based filters to re-weight RFM feature importances and identify those features that are most indicative of low cellular viability. Our resulting pipeline is computationally efficient, taking under 3 minutes for analyzing all 17, 453 knockouts from DepMap for candidate SL pairs. We show that our pipeline more accurately recovers experimentally verified SL pairs than prior approaches. Moreover, our pipeline finds new candidate SL pairs, thereby opening novel avenues for identifying genetic vulnerabilities in cancer.

Published
2023
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