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202. Gene expression profiling to study racial differences after heart transplantation

Author

Khush, Kiran K., primary, Pham, Michael X., additional, Teuteberg, Jeffrey J., additional, Kfoury, Abdallah G., additional, Deng, Mario C., additional, Kao, Andrew, additional, Anderson, Allen S., additional, Cotts, William G., additional, Ewald, Gregory A., additional, Baran, David A., additional, Hiller, David, additional, Yee, James, additional, and Valantine, Hannah A., additional

Published
2015
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203. Outcomes of Biventricular Mechanical Support Patients Discharged to Home to Await Heart Transplantation

Author

Creaser, Julie W., primary, Rourke, Darlene, additional, Vandenbogaart, Elizabeth, additional, Chaker, Tamara, additional, Nsair, Ali, additional, Cheng, Richard, additional, Fonarow, Gregg, additional, Livingston, Nancy, additional, Howell, Elan, additional, Huie, Newman, additional, Baas, Arnold S., additional, Deng, Mario, additional, Hickey, Ann, additional, Shemin, Richard J., additional, and MacLellan, W. Robb, additional

Published
2015
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204. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial

Author

Ardehali, Abbas, primary, Esmailian, Fardad, additional, Deng, Mario, additional, Soltesz, Edward, additional, Hsich, Eileen, additional, Naka, Yoshifumi, additional, Mancini, Donna, additional, Camacho, Margarita, additional, Zucker, Mark, additional, Leprince, Pascal, additional, Padera, Robert, additional, and Kobashigawa, Jon, additional

Published
2015
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206. LBP24

Author

Korin, Yael, primary, Wisniewski, Nicholas, additional, Cadeiras, Martin, additional, Schaenman, Joanna, additional, Kwon, Murray, additional, Sidwell, Tiffany, additional, Kandarian, Fadi, additional, Bondar, Galyna, additional, Reed, Elaine, additional, and Deng, Mario, additional

Published
2015
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207. Characterization of ventricular assist device–mediated sensitization in the bridge-to-heart-transplantation patient

Author

Kwon, Murray H., primary, Zhang, Jennifer Q., additional, Schaenman, Joanna M., additional, Cadeiras, Martin, additional, Gjertson, David W., additional, Krystal, Carolyn A., additional, Laks, Hillel, additional, Ardehali, Abbas, additional, Deng, Mario C., additional, Shemin, Richard J., additional, and Reed, Elaine F., additional

Published
2015
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209. Unexplained Graft Dysfunction after Heart Transplantation—Role of Novel Molecular Expression Test Score and QTc-Interval: A Case Report

Author

Shahzad, Khurram, Cadeiras, Martin, Arai, Kotaro, Abramov, Dmitry, Burke, Elizabeth, and Deng, Mario C.

Subjects
surgical procedures, operative, Article Subject
Abstract

In the current era of immunosuppressive medications there is increased observed incidence of graft dysfunction in the absence of known histological criteria of rejection after heart transplantation. A noninvasive molecular expression diagnostic test was developed and validated to rule out histological acute cellular rejection. In this paper we present for the first time, longitudinal pattern of changes in this novel diagnostic test score along with QTc-interval in a patient who was admitted with unexplained graft dysfunction. Patient presented with graft failure with negative findings on all known criteria of rejection including acute cellular rejection, antibody mediated rejection and cardiac allograft vasculopathy. The molecular expression test score showed gradual increase and QTc-interval showed gradual prolongation with the gradual decline in graft function. This paper exemplifies that in patients presenting with unexplained graft dysfunction, GEP test score and QTc-interval correlate with the changes in the graft function.

Published
2010
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210. Molecular- and organelle-based predictive paradigm underlying recovery by left ventricular assist device support

Author

Liem, David A, Nsair, Ali, Setty, Shaun P, Cadeiras, Martin, Wang, Ding, Maclellan, Robb, Lotz, Chris, Lin, Amanda J, Tabaraki, Jason, Li, Hua, Ge, Junbo, Odeberg, Jacob, Pontén, Fredrik, Larsson, Erik, Mulder, Jan, Lundberg, Emma, Weiss, James N, Uhlen, Mathias, Ping, Peipei, Deng, Mario C, Liem, David A, Nsair, Ali, Setty, Shaun P, Cadeiras, Martin, Wang, Ding, Maclellan, Robb, Lotz, Chris, Lin, Amanda J, Tabaraki, Jason, Li, Hua, Ge, Junbo, Odeberg, Jacob, Pontén, Fredrik, Larsson, Erik, Mulder, Jan, Lundberg, Emma, Weiss, James N, Uhlen, Mathias, Ping, Peipei, and Deng, Mario C

Published
2014
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211. An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

Author

Brownstein, Catherine A., Beggs, Alan H., Homer, Nils, Merriman, Barry, Yu, Timothy W., Flannery, Katherine C., DeChene, Elizabeth T., Towne, Meghan C., Savage, Sarah K., Price, Emily N., Holm, Ingrid A., Luquette, Lovelace J., Lyon, Elaine, Majzoub, Joseph, Neupert, Peter, McCallie, David, Jr., Szolovits, Peter, Willard, Huntington F., Mendelsohn, Nancy J., Temme, Renee, Finkel, Richard S., Yum, Sabrina W., Medne, Livija, Sunyaev, Shamil R., Adzhubey, Ivan, Cassa, Christopher A., de Bakker, Paul I. W., Duzkale, Hatice, Dworzynski, Piotr, Fairbrother, William, Francioli, Laurent, Funke, Birgit H., Giovanni, Monica A., Handsaker, Robert E., Lage, Kasper, Lebo, Matthew S., Lek, Monkol, Leshchiner, Ignaty, MacArthur, Daniel G., McLaughlin, Heather M., Murray, Michael F., Pers, Tune H., Polak, Paz P., Raychaudhuri, Soumya, Rehm, Heidi L., Soemedi, Rachel, Stitziel, Nathan O., Vestecka, Sara, Supper, Jochen, Gugenmus, Claudia, Klocke, Bernward, Hahn, Alexander, Schubach, Max, Menzel, Mortiz, Biskup, Saskia, Freisinger, Peter, Deng, Mario, Braun, Martin, Perner, Sven, Smith, Richard J. H., Andorf, Janeen L., Huang, Jian, Ryckman, Kelli, Sheffield, Val C., Stone, Edwin M., Bair, Thomas, Black-Ziegelbein, E. Ann, Braun, Terry A., Darbro, Benjamin, DeLuca, Adam P., Kolbe, Diana L., Scheetz, Todd E., Shearer, Aiden E., Sompallae, Rama, Wang, Kai, Bassuk, Alexander G., Edens, Erik, Mathews, Katherine, Moore, Steven A., Shchelochkov, Oleg A., Trapane, Pamela, Bossler, Aaron, Campbell, Colleen A., Heusel, Jonathan W., Kwitek, Anne, Maga, Tara, Panzer, Karin, Wassink, Thomas, Van Daele, Douglas, Azaiez, Hela, Booth, Kevin, Meyer, Nic, Segal, Michael M., Williams, Marc S., Tromp, Gerard, White, Peter, Corsmeier, Donald, Fitzgerald-Butt, Sara, Herman, Gail, Lamb-Thrush, Devon, McBride, Kim L., Newsom, David, Pierson, Christopher R., Rakowsky, Alexander T., Maver, Ales, Lovrecic, Luca, Palandacic, Anja, Peterlin, Borut, Torkamani, Ali, Wedell, Anna, Huss, Mikael, Alexeyenko, Andrey, Lindvall, Jessica M., Magnusson, Mans, Nilsson, Daniel, Stranneheim, Henrik, Taylan, Fulya, Gilissen, Christian, Hoischen, Alexander, van Bon, Bregje, Yntema, Helger, Nelen, Marcel, Zhang, Weidong, Sager, Jason, Zhang, Lu, Blair, Kathryn, Kural, Deniz, Cariaso, Michael, Lennon, Greg G., Javed, Asif, Agrawal, Saloni, Ng, Pauline C., Sandhu, Komal S., Krishna, Shuba, Veeramachaneni, Vamsi, Isakov, Ofer, Halperin, Eran, Friedman, Eitan, Shomron, Noam, Glusman, Gustavo, Roach, Jared C., Caballero, Juan, Cox, Hannah C., Mauldin, Denise, Ament, Seth A., Rowen, Lee, Richards, Daniel R., San Lucas, F. Anthony, Gonzalez-Garay, Manuel L., Caskey, C. Thomas, Bai, Yu, Huang, Ying, Fang, Fang, Zhang, Yan, Wang, Zhengyuan, Barrera, Jorge, Garcia-Lobo, Juan M., Gonzalez-Lamuno, Domingo, Llorca, Javier, Rodriguez, Maria C., Varela, Ignacio, Reese, Martin G., De la Vega, Francisco M., Kiruluta, Edward, Cargill, Michele, Hart, Reece K., Sorenson, Jon M., Lyon, Gholson J., Stevenson, David A., Bray, Bruce E., Moore, Barry M., Eilbeck, Karen, Yandell, Mark, Zhao, Hongyu, Hou, Lin, Chen, Xiaowei, Yan, Xiting, Chen, Mengjie, Li, Cong, Yang, Can, Gunel, Murat, Li, Peining, Kong, Yong, Alexander, Austin C., Albertyn, Zayed I., Boycott, Kym M., Bulman, Dennis E., Gordon, Paul M. K., Innes, A. Micheil, Knoppers, Bartha M., Majewski, Jacek, Marshall, Christian R., Parboosingh, Jillian S., Sawyer, Sarah L., Samuels, Mark E., Schwartzentruber, Jeremy, Kohane, Isaac S., Margulies, David M., Brownstein, Catherine A., Beggs, Alan H., Homer, Nils, Merriman, Barry, Yu, Timothy W., Flannery, Katherine C., DeChene, Elizabeth T., Towne, Meghan C., Savage, Sarah K., Price, Emily N., Holm, Ingrid A., Luquette, Lovelace J., Lyon, Elaine, Majzoub, Joseph, Neupert, Peter, McCallie, David, Jr., Szolovits, Peter, Willard, Huntington F., Mendelsohn, Nancy J., Temme, Renee, Finkel, Richard S., Yum, Sabrina W., Medne, Livija, Sunyaev, Shamil R., Adzhubey, Ivan, Cassa, Christopher A., de Bakker, Paul I. W., Duzkale, Hatice, Dworzynski, Piotr, Fairbrother, William, Francioli, Laurent, Funke, Birgit H., Giovanni, Monica A., Handsaker, Robert E., Lage, Kasper, Lebo, Matthew S., Lek, Monkol, Leshchiner, Ignaty, MacArthur, Daniel G., McLaughlin, Heather M., Murray, Michael F., Pers, Tune H., Polak, Paz P., Raychaudhuri, Soumya, Rehm, Heidi L., Soemedi, Rachel, Stitziel, Nathan O., Vestecka, Sara, Supper, Jochen, Gugenmus, Claudia, Klocke, Bernward, Hahn, Alexander, Schubach, Max, Menzel, Mortiz, Biskup, Saskia, Freisinger, Peter, Deng, Mario, Braun, Martin, Perner, Sven, Smith, Richard J. H., Andorf, Janeen L., Huang, Jian, Ryckman, Kelli, Sheffield, Val C., Stone, Edwin M., Bair, Thomas, Black-Ziegelbein, E. Ann, Braun, Terry A., Darbro, Benjamin, DeLuca, Adam P., Kolbe, Diana L., Scheetz, Todd E., Shearer, Aiden E., Sompallae, Rama, Wang, Kai, Bassuk, Alexander G., Edens, Erik, Mathews, Katherine, Moore, Steven A., Shchelochkov, Oleg A., Trapane, Pamela, Bossler, Aaron, Campbell, Colleen A., Heusel, Jonathan W., Kwitek, Anne, Maga, Tara, Panzer, Karin, Wassink, Thomas, Van Daele, Douglas, Azaiez, Hela, Booth, Kevin, Meyer, Nic, Segal, Michael M., Williams, Marc S., Tromp, Gerard, White, Peter, Corsmeier, Donald, Fitzgerald-Butt, Sara, Herman, Gail, Lamb-Thrush, Devon, McBride, Kim L., Newsom, David, Pierson, Christopher R., Rakowsky, Alexander T., Maver, Ales, Lovrecic, Luca, Palandacic, Anja, Peterlin, Borut, Torkamani, Ali, Wedell, Anna, Huss, Mikael, Alexeyenko, Andrey, Lindvall, Jessica M., Magnusson, Mans, Nilsson, Daniel, Stranneheim, Henrik, Taylan, Fulya, Gilissen, Christian, Hoischen, Alexander, van Bon, Bregje, Yntema, Helger, Nelen, Marcel, Zhang, Weidong, Sager, Jason, Zhang, Lu, Blair, Kathryn, Kural, Deniz, Cariaso, Michael, Lennon, Greg G., Javed, Asif, Agrawal, Saloni, Ng, Pauline C., Sandhu, Komal S., Krishna, Shuba, Veeramachaneni, Vamsi, Isakov, Ofer, Halperin, Eran, Friedman, Eitan, Shomron, Noam, Glusman, Gustavo, Roach, Jared C., Caballero, Juan, Cox, Hannah C., Mauldin, Denise, Ament, Seth A., Rowen, Lee, Richards, Daniel R., San Lucas, F. Anthony, Gonzalez-Garay, Manuel L., Caskey, C. Thomas, Bai, Yu, Huang, Ying, Fang, Fang, Zhang, Yan, Wang, Zhengyuan, Barrera, Jorge, Garcia-Lobo, Juan M., Gonzalez-Lamuno, Domingo, Llorca, Javier, Rodriguez, Maria C., Varela, Ignacio, Reese, Martin G., De la Vega, Francisco M., Kiruluta, Edward, Cargill, Michele, Hart, Reece K., Sorenson, Jon M., Lyon, Gholson J., Stevenson, David A., Bray, Bruce E., Moore, Barry M., Eilbeck, Karen, Yandell, Mark, Zhao, Hongyu, Hou, Lin, Chen, Xiaowei, Yan, Xiting, Chen, Mengjie, Li, Cong, Yang, Can, Gunel, Murat, Li, Peining, Kong, Yong, Alexander, Austin C., Albertyn, Zayed I., Boycott, Kym M., Bulman, Dennis E., Gordon, Paul M. K., Innes, A. Micheil, Knoppers, Bartha M., Majewski, Jacek, Marshall, Christian R., Parboosingh, Jillian S., Sawyer, Sarah L., Samuels, Mark E., Schwartzentruber, Jeremy, Kohane, Isaac S., and Margulies, David M.

Abstract

Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups., QC 20140819

Published
2014
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212. Comparison of whole blood and peripheral blood mononuclear cell gene expression for evaluation of the perioperative inflammatory response in patients with advanced heart failure.

Author

Bondar, Galyna, Bondar, Galyna, Cadeiras, Martin, Wisniewski, Nicholas, Maque, Jetrina, Chittoor, Jay, Chang, Eleanor, Bakir, Maral, Starling, Charlotte, Shahzad, Khurram, Ping, Peipei, Reed, Elaine, Deng, Mario, Bondar, Galyna, Bondar, Galyna, Cadeiras, Martin, Wisniewski, Nicholas, Maque, Jetrina, Chittoor, Jay, Chang, Eleanor, Bakir, Maral, Starling, Charlotte, Shahzad, Khurram, Ping, Peipei, Reed, Elaine, and Deng, Mario

Abstract

BackgroundHeart failure (HF) prevalence is increasing in the United States. Mechanical Circulatory Support (MCS) therapy is an option for Advanced HF (AdHF) patients. Perioperatively, multiorgan dysfunction (MOD) is linked to the effects of device implantation, augmented by preexisting HF. Early recognition of MOD allows for better diagnosis, treatment, and risk prediction. Gene expression profiling (GEP) was used to evaluate clinical phenotypes of peripheral blood mononuclear cells (PBMC) transcriptomes obtained from patients' blood samples. Whole blood (WB) samples are clinically more feasible, but their performance in comparison to PBMC samples has not been determined.MethodsWe collected blood samples from 31 HF patients (57±15 years old) undergoing cardiothoracic surgery and 7 healthy age-matched controls, between 2010 and 2011, at a single institution. WB and PBMC samples were collected at a single timepoint postoperatively (median day 8 postoperatively) (25-75% IQR 7-14 days) and subjected to Illumina single color Human BeadChip HT12 v4 whole genome expression array analysis. The Sequential Organ Failure Assessment (SOFA) score was used to characterize the severity of MOD into low (≤ 4 points), intermediate (5-11), and high (≥ 12) risk categories correlating with GEP.ResultsResults indicate that the direction of change in GEP of individuals with MOD as compared to controls is similar when determined from PBMC versus WB. The main enriched terms by Gene Ontology (GO) analysis included those involved in the inflammatory response, apoptosis, and other stress response related pathways. The data revealed 35 significant GO categories and 26 pathways overlapping between PBMC and WB. Additionally, class prediction using machine learning tools demonstrated that the subset of significant genes shared by PBMC and WB are sufficient to train as a predictor separating the SOFA groups.ConclusionGEP analysis of WB has the potential to become a clinical tool for immune-monitori

Published
2014

213. Action potential-evoked calcium release is impaired in single skeletal muscle fibers from heart failure patients.

Author

DiFranco, Marino, DiFranco, Marino, Quiñonez, Marbella, Shieh, Perry, Fonarow, Gregg C, Cruz, Daniel, Deng, Mario C, Vergara, Julio L, Middlekauff, Holly R, DiFranco, Marino, DiFranco, Marino, Quiñonez, Marbella, Shieh, Perry, Fonarow, Gregg C, Cruz, Daniel, Deng, Mario C, Vergara, Julio L, and Middlekauff, Holly R

Abstract

BackgroundExercise intolerance in chronic heart failure (HF) has been attributed to abnormalities of the skeletal muscles. Muscle function depends on intact excitation-contraction coupling (ECC), but ECC studies in HF models have been inconclusive, due to deficiencies in the animal models and tools used to measure calcium (Ca2+) release, mandating investigations in skeletal muscle from HF patients. The purpose of this study was to test the hypothesis that Ca2+ release is significantly impaired in the skeletal muscle of HF patients in whom exercise capacity is severely diminished compared to age-matched healthy volunteers.Methods and findingsUsing state-of-the-art electrophysiological and optical techniques in single muscle fibers from biopsies of the locomotive vastus lateralis muscle, we measured the action potential (AP)-evoked Ca2+ release in 4 HF patients and 4 age-matched healthy controls. The mean peak Ca2+ release flux in fibers obtained from HF patients (10±1.2 µM/ms) was markedly (2.6-fold) and significantly (p<0.05) smaller than in fibers from healthy volunteers (28±3.3 µM/ms). This impairment in AP-evoked Ca2+ release was ubiquitous and was not explained by differences in the excitability mechanisms since single APs were indistinguishable between HF patients and healthy volunteers.ConclusionsThese findings prove the feasibility of performing electrophysiological experiments in single fibers from human skeletal muscle, and offer a new approach for investigations of myopathies due to HF and other diseases. Importantly, we have demonstrated that one step in the ECC process, AP-evoked Ca2+ release, is impaired in single muscle fibers in HF patients.

Published
2014

214. An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

Author

Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Szolovits, Peter, Brownstein, Catherine A., Beggs, Alan H., Homer, Nils, Merriman, Barry, Yu, Timothy W., Flannery, Katherine C., DeChene, Elizabeth T., Towne, Meghan C., Savage, Sarah K., Price, Emily N., Holm, Ingrid A., Luquette, Lovelace J., Lyon, Elaine, Majzoub, Joseph, Neupert, Peter, McCallie Jr., David, Willard, Huntington F., Mendelsohn, Nancy J., Temme, Renee, Finkel, Richard S., Yum, Sabrina W., Medne, Livija, Sunyaev, Shamil R., Adzhubey, Ivan, Cassa, Christopher A., de Bakker, Paul I. W., Duzkale, Hatice, Dworzyński, Piotr, Fairbrother, William G., Francioli, Laurent, Funke, Birgit H., Giovanni, Monica A., Handsaker, Robert E., Lage, Kasper, Lebo, Matthew S., Lek, Monkol, Leshchiner, Ignaty, MacArthur, Daniel G., McLaughlin, Heather M., Murray, Michael F., Pers, Tune H., Polak, Paz P., Raychaudhuri, Soumya, Rehm, Heidi L., Soemedi, Rachel, Stitziel, Nathan O., Vestecka, Sara, Supper, Jochen, Gugenmus, Claudia, Klocke, Bernward, Hahn, Alexander, Schubach, Max, Menzel, Mortiz, Biskup, Saskia, Freisinger, Peter, Deng, Mario, Braun, Martin, Perner, Sven, Smith, Richard J. H., Andorf, Janeen L., Huang, Jian, Ryckman, Kelli, Sheffield, Val C., Stone, Edwin M., Bair, Thomas, Black-Ziegelbein, E. A., Braun, Terry A., Darbro, Benjamin, DeLuca, Adam P., Kolbe, Diana L., Scheetz, Todd E., Shearer, Aiden E., Sompallae, Rama, Wang, Kai, Bassuk, Alexander G., Edens, Erik, Mathews, Katherine, Moore, Steven A., Shchelochkov, Oleg A., Trapane, Pamela, Bossler, Aaron, Campbell, Colleen A., Heusel, Jonathan W., Kwitek, Anne, Maga, Tara, Panzer, Karin, Wassink, Thomas, Van Daele, Douglas, Azaiez, Hela, Booth, Kevin, Meyer, Nic, Segal, Michael M., Williams, Marc S., Tromp, Gerard, White, Peter, Corsmeier, Donald, Fitzgerald-Butt, Sara, Herman, Gail, Lamb-Thrush, Devon, McBride, Kim L., Newsom, David, Pierson, Christopher R., Rakowsky, Alexander T., Maver, Ales, Lovrečić, Luca, Palandacic, Anja, Peterlin, Borut, Torkamani, Ali, Wedell, Anna, Huss, Mikael, Alexeyenko, Andrey, Lindvall, Jessica M., Magnusson, Mans, Nilsson, Daniel, Stranneheim, Henrik, Taylan, Fulya, Gilissen, Christian, Hoischen, Alexander, van Bon, Bregje, Yntema, Helger, Nelen, Marcel, Zhang, Weidong, Sager, Jason, Zhang, Lu, Blair, Kathryn, Kural, Deniz, Cariaso, Michael, Lennon, Greg G., Javed, Asif, Agrawal, Saloni, Ng, Pauline C., Sandhu, Komal S., Krishna, Shuba, Veeramachaneni, Vamsi, Isakov, Ofer, Halperin, Eran, Friedman, Eitan, Shomron, Noam, Glusman, Gustavo, Roach, Jared C., Caballero, Juan, Cox, Hannah C., Mauldin, Denise, Ament, Seth A., Rowen, Lee, Richards, Daniel R., Lucas, F Anthony S., Gonzalez-Garay, Manuel L., Caskey, C. T., Bai, Yu, Huang, Ying, Fang, Fang, Zhang, Yan, Wang, Zhengyuan, Barrera, Jorge, Garcia-Lobo, Juan M., González-Lamuno, Domingo, Llorca, Javier, Rodriguez, Maria C., Varela, Ignacio, Reese, Martin G., De La Vega, Francisco M., Kiruluta, Edward, Cargill, Michele, Hart, Reece K., Sorenson, Jon M., Lyon, Gholson J., Stevenson, David A., Bray, Bruce E., Moore, Barry M., Eilbeck, Karen, Yandell, Mark, Zhao, Hongyu, Hou, Lin, Chen, Xiaowei, Yan, Xiting, Chen, Mengjie, Li, Cong, Yang, Can, Gunel, Murat, Li, Peining, Kong, Yong, Alexander, Austin C., Albertyn, Zayed I., Boycott, Kym M., Bulman, Dennis E., Gordon, Paul M. K., Innes, A. M., Knoppers, Bartha M., Majewski, Jacek, Marshall, Christian R., Parboosingh, Jillian S., Sawyer, Sarah L., Samuels, Mark E., Schwartzentruber, Jeremy, Kohane, Isaac, Margulies, David M., Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Szolovits, Peter, Brownstein, Catherine A., Beggs, Alan H., Homer, Nils, Merriman, Barry, Yu, Timothy W., Flannery, Katherine C., DeChene, Elizabeth T., Towne, Meghan C., Savage, Sarah K., Price, Emily N., Holm, Ingrid A., Luquette, Lovelace J., Lyon, Elaine, Majzoub, Joseph, Neupert, Peter, McCallie Jr., David, Willard, Huntington F., Mendelsohn, Nancy J., Temme, Renee, Finkel, Richard S., Yum, Sabrina W., Medne, Livija, Sunyaev, Shamil R., Adzhubey, Ivan, Cassa, Christopher A., de Bakker, Paul I. W., Duzkale, Hatice, Dworzyński, Piotr, Fairbrother, William G., Francioli, Laurent, Funke, Birgit H., Giovanni, Monica A., Handsaker, Robert E., Lage, Kasper, Lebo, Matthew S., Lek, Monkol, Leshchiner, Ignaty, MacArthur, Daniel G., McLaughlin, Heather M., Murray, Michael F., Pers, Tune H., Polak, Paz P., Raychaudhuri, Soumya, Rehm, Heidi L., Soemedi, Rachel, Stitziel, Nathan O., Vestecka, Sara, Supper, Jochen, Gugenmus, Claudia, Klocke, Bernward, Hahn, Alexander, Schubach, Max, Menzel, Mortiz, Biskup, Saskia, Freisinger, Peter, Deng, Mario, Braun, Martin, Perner, Sven, Smith, Richard J. H., Andorf, Janeen L., Huang, Jian, Ryckman, Kelli, Sheffield, Val C., Stone, Edwin M., Bair, Thomas, Black-Ziegelbein, E. A., Braun, Terry A., Darbro, Benjamin, DeLuca, Adam P., Kolbe, Diana L., Scheetz, Todd E., Shearer, Aiden E., Sompallae, Rama, Wang, Kai, Bassuk, Alexander G., Edens, Erik, Mathews, Katherine, Moore, Steven A., Shchelochkov, Oleg A., Trapane, Pamela, Bossler, Aaron, Campbell, Colleen A., Heusel, Jonathan W., Kwitek, Anne, Maga, Tara, Panzer, Karin, Wassink, Thomas, Van Daele, Douglas, Azaiez, Hela, Booth, Kevin, Meyer, Nic, Segal, Michael M., Williams, Marc S., Tromp, Gerard, White, Peter, Corsmeier, Donald, Fitzgerald-Butt, Sara, Herman, Gail, Lamb-Thrush, Devon, McBride, Kim L., Newsom, David, Pierson, Christopher R., Rakowsky, Alexander T., Maver, Ales, Lovrečić, Luca, Palandacic, Anja, Peterlin, Borut, Torkamani, Ali, Wedell, Anna, Huss, Mikael, Alexeyenko, Andrey, Lindvall, Jessica M., Magnusson, Mans, Nilsson, Daniel, Stranneheim, Henrik, Taylan, Fulya, Gilissen, Christian, Hoischen, Alexander, van Bon, Bregje, Yntema, Helger, Nelen, Marcel, Zhang, Weidong, Sager, Jason, Zhang, Lu, Blair, Kathryn, Kural, Deniz, Cariaso, Michael, Lennon, Greg G., Javed, Asif, Agrawal, Saloni, Ng, Pauline C., Sandhu, Komal S., Krishna, Shuba, Veeramachaneni, Vamsi, Isakov, Ofer, Halperin, Eran, Friedman, Eitan, Shomron, Noam, Glusman, Gustavo, Roach, Jared C., Caballero, Juan, Cox, Hannah C., Mauldin, Denise, Ament, Seth A., Rowen, Lee, Richards, Daniel R., Lucas, F Anthony S., Gonzalez-Garay, Manuel L., Caskey, C. T., Bai, Yu, Huang, Ying, Fang, Fang, Zhang, Yan, Wang, Zhengyuan, Barrera, Jorge, Garcia-Lobo, Juan M., González-Lamuno, Domingo, Llorca, Javier, Rodriguez, Maria C., Varela, Ignacio, Reese, Martin G., De La Vega, Francisco M., Kiruluta, Edward, Cargill, Michele, Hart, Reece K., Sorenson, Jon M., Lyon, Gholson J., Stevenson, David A., Bray, Bruce E., Moore, Barry M., Eilbeck, Karen, Yandell, Mark, Zhao, Hongyu, Hou, Lin, Chen, Xiaowei, Yan, Xiting, Chen, Mengjie, Li, Cong, Yang, Can, Gunel, Murat, Li, Peining, Kong, Yong, Alexander, Austin C., Albertyn, Zayed I., Boycott, Kym M., Bulman, Dennis E., Gordon, Paul M. K., Innes, A. M., Knoppers, Bartha M., Majewski, Jacek, Marshall, Christian R., Parboosingh, Jillian S., Sawyer, Sarah L., Samuels, Mark E., Schwartzentruber, Jeremy, Kohane, Isaac, and Margulies, David M.

Abstract

Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups., Boston Children's Hospital (Manton Center for Orphan Disease Research), Harvard Medical School (Center for Biomedical Infomatics)

Published
2014

215. Comparison of Whole Blood and Peripheral Blood Mononuclear Cell Gene Expression for Evaluation of the Perioperative Inflammatory Response in Patients with Advanced Heart Failure

Author

Bondar, Galyna, primary, Cadeiras, Martin, additional, Wisniewski, Nicholas, additional, Maque, Jetrina, additional, Chittoor, Jay, additional, Chang, Eleanor, additional, Bakir, Maral, additional, Starling, Charlotte, additional, Shahzad, Khurram, additional, Ping, Peipei, additional, Reed, Elaine, additional, and Deng, Mario, additional

Published
2014
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219. Integrative model of leukocyte genomics and organ dysfunction in heart failure patients requiring mechanical circulatory support: a prospective observational study.

Author

Wisniewski, Nicholas, Bondar, Galyna, Rau, Christoph, Chittoor, Jay, Chang, Eleanor, Esmaeili, Azadeh, Cadeiras, Martin, and Deng, Mario

Subjects
LEUCOCYTES, HEART failure patients, SYSTEMIC inflammatory response syndrome, MESSENGER RNA, GENE ontology
Abstract

Background: The implantation of mechanical circulatory support devices in heart failure patients is associated with a systemic inflammatory response, potentially leading to death from multiple organ dysfunction syndrome. Previous studies point to the involvement of many mechanisms, but an integrative hypothesis does not yet exist. Using time-dependent whole-genome mRNA expression in circulating leukocytes, we constructed a systems-model to improve mechanistic understanding and prediction of adverse outcomes. Methods: We sampled peripheral blood mononuclear cells from 22 consecutive patients undergoing mechanical circulatory support device (MCS) surgery, at 5 timepoints: day -1 preoperative, and postoperative days 1, 3, 5 and 8. Clinical phenotyping was performed using 12 clinical parameters, 2 organ dysfunction scoring systems, and survival outcomes. We constructed a strictly phenotype-driven time-dependent non-supervised systemsrepresentation using weighted gene co-expression network analysis, and annotated eigengenes using gene ontology, pathway, and transcription factor binding site enrichment analyses. Genes and eigengenes were mapped to the clinical phenotype using a linear mixed-effect model, with Cox models also fit at each timepoint to survival outcomes. Results: We inferred a 19-module network, in which most module eigengenes correlated with at least one aspect of the clinical phenotype. We observed a response of advanced heart failure patients to surgery orchestrated into stages: first, activation of the innate immune response, followed by anti-inflammation, and finally reparative processes such as mitosis, coagulation and apoptosis. Eigengenes related to red blood cell production and extracellular matrix degradation became predictors of survival late in the timecourse corresponding to multiorgan dysfunction and disseminated intravascular coagulation. Conclusions: Our model provides an integrative representation of leukocyte biology during the systemic inflammatory response following MCS device implantation. It demonstrates consistency with previous hypotheses, identifying a number of known mechanisms. At the same time, it suggests novel hypotheses about time-specific targets. [ABSTRACT FROM AUTHOR]

Published
2017
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220. Evaluation of the SIPAT instrument to assess psychosocial risk in heart transplant candidates: A retrospective single center study.

Author

Vandenbogaart, Elizabeth, Doering, Lynn, Chen, Belinda, Saltzman, Ann, Chaker, Tamara, Creaser, Julie W., Rourke, Darlene, Cheng, Richard W., Fonarow, Gregg C., and Deng, Mario

Abstract

Objectives We evaluated the reliability of the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) in heart transplant (HT) recipients and explored its usefulness in predicting post-transplant outcomes. Background Pre-transplant psychosocial and behavioral risk is associated with post-transplant clinical outcomes. SIPAT is a risk assessment tool created for pre-transplant psychosocial evaluation. Methods Via retrospective chart review, three examiners applied the SIPAT to 51 adult HT recipients. Examiners blinded to SIPAT scores extracted data and interviewed clinicians for one-year post-transplant outcomes. Analysis included Intra-class correlation coefficient (ICC), Pearson's correlation coefficient and Chi-square. Results SIPAT demonstrated strong inter-rater reliability (ICC = 0.89, 95% CI = 0.76–0.96). Compared to those with SIPAT ratings of “Excellent/Good”, the “Minimally Acceptable Candidate/High Risk” group was more likely to miss clinic visits ( p = 0.004). Conclusions The SIPAT tool had strong IRR. Less favorable SIPAT ratings were associated with nonadherence to clinic visits. Further study is warranted to determine association of SIPAT ratings to clinical outcomes. [ABSTRACT FROM AUTHOR]

Published
2017
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221. Cardiac Amyloidosis: Diagnosis and Treatment Strategies.

Author

Tuzovic, Mirela, Yang, Eric, Baas, Arnold, Depasquale, Eugene, Deng, Mario, Cruz, Daniel, and Vorobiof, Gabriel

Abstract

Cardiac amyloidosis in the United States is most often due to myocardial infiltration by immunoglobulin protein, such as in AL amyloidosis, or by the protein transthyretin, such as in hereditary and senile amyloidosis. Cardiac amyloidosis often portends a poor prognosis especially in patients with systemic AL amyloidosis. Despite better understanding of the pathophysiology of amyloid, many patients are still diagnosed late in the disease course. This review investigates the current understanding and new research on the diagnosis and treatment strategies in patients with cardiac amyloidosis. Myocardial amyloid infiltration distribution occurs in a variety of patterns. Structural and functional changes on echocardiography can suggest presence of amyloid, but CMR and nuclear imaging provide important complementary information on amyloid burden and the amyloid subtype, respectively. While for AL amyloid, treatment success largely depends on early diagnosis, for ATTR amyloid, new investigational agents that reduce production of transthyretin protein may have significant impact on clinical outcomes. Advancements in the non-invasive diagnostic detection and improvements in early disease recognition will undoubtedly facilitate a larger proportion of patients to receive early therapy when it is most effective. [ABSTRACT FROM AUTHOR]

Published
2017
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222. The AlloMap™ genomic biomarker story: 10 years after.

Author

Deng, Mario C.

Subjects
*HEART transplantation, *GRAFT rejection, *BIOMARKERS, *GENE expression profiling, *ALGORITHMS
Abstract

Over the last >20 years, we have co-developed the rationale for the first diagnostic and prognostic leukocyte gene expression profiling ( GEP) biomarker test in transplantation medicine that gained US- FDA-regulatory clearance and international evidence-based medicine guideline acceptance to rule out moderate/severe acute cellular cardiac allograft rejection without invasive endomyocardial biopsies ( EMB). Based on this test, a non-invasive clinical algorithm was implemented since 2005. After clinical implementation, this GEP-based monitoring in direct comparison with an EMB-based strategy was non-inferior with respect to detection of clinical rejection, defined as new onset allograft dysfunction with/without histology of ACR, re-transplantation or death, and at the same time improved patient satisfaction. Subsequently, we demonstrated the test's capacity when used as serial monitoring tool to predict these clinical rejection events. In this Personal Viewpoint article, I will discuss the various decision-making branching points that were made in the AlloMap biomarker test development to inform future genomic biomarker test development projects. [ABSTRACT FROM AUTHOR]

Published
2017
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226. Clinical outcomes and risk factors of coronary artery aneurysms after successful percutaneous coronary intervention and drug-eluting stent implantation for chronic total occlusions

Author

Zhong, Xin, primary, Li, Hua, additional, Li, Chenguang, additional, Zong, Nobel, additional, Liem, David, additional, Chan, X'avia, additional, Zhang, Shuning, additional, Zhang, Youen, additional, Wang, Xinggang, additional, Wu, Xing, additional, Zhang, Wenbin, additional, Yao, Kang, additional, Liu, Xuebo, additional, Ge, Lei, additional, Hu, Kai, additional, Qian, Juying, additional, Deng, Mario, additional, and Ge, Junbo, additional

Published
2014
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233. CARDIAC RETRANSPLANTATION: HOW FAR HAVE WE COME?

Author

DePasquale, Eugene Christopher, primary, Cheng, Richard, additional, Nsair, Ali, additional, Reardon, Leigh, additional, Baas, Arnold, additional, Cadeiras, Martin, additional, Cruz, Daniel, additional, Halnon, Nancy, additional, Alejos, Juan, additional, Deng, Mario, additional, Laks, Hillel, additional, and Ardehali, Abbas, additional

Published
2014
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234. Utility of Gene Expression Profiling Score Variability to Predict Clinical Events in Heart Transplant Recipients

Author

Deng, Mario C., primary, Elashoff, Barbara, additional, Pham, Michael X., additional, Teuteberg, Jeffrey J., additional, Kfoury, Abdallah G., additional, Starling, Randall C., additional, Cappola, Thomas P., additional, Kao, Andrew, additional, Anderson, Allen S., additional, Cotts, William G., additional, Ewald, Gregory A., additional, Baran, David A., additional, Bogaev, Roberta C., additional, Shahzad, Khurram, additional, Hiller, David, additional, Yee, James, additional, and Valantine, Hannah A., additional

Published
2014
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235. Protein kinetic signatures of the remodeling heart following isoproterenol stimulation

Author

Lam, Maggie P.Y., primary, Wang, Ding, additional, Lau, Edward, additional, Liem, David A., additional, Kim, Allen K., additional, Ng, Dominic C.M., additional, Liang, Xiangbo, additional, Bleakley, Brian J., additional, Liu, Chenguang, additional, Tabaraki, Jason D., additional, Cadeiras, Martin, additional, Wang, Yibin, additional, Deng, Mario C., additional, and Ping, Peipei, additional

Published
2014
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236. Molecular- and Organelle-Based Predictive Paradigm Underlying Recovery by Left Ventricular Assist Device Support

Author

Liem, David A., primary, Nsair, Ali, additional, Setty, Shaun P., additional, Cadeiras, Martin, additional, Wang, Ding, additional, Maclellan, Robb, additional, Lotz, Chris, additional, Lin, Amanda J., additional, Tabaraki, Jason, additional, Li, Hua, additional, Ge, Junbo, additional, Odeberg, Jacob, additional, Ponten, Fredrik, additional, Larson, Erik, additional, Mulder, Jan, additional, Lundberg, Emma, additional, Weiss, James N., additional, Uhlen, Mathias, additional, Ping, Peipei, additional, and Deng, Mario C., additional

Published
2014
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239. An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

Author

Brownstein, Catherine A, primary, Beggs, Alan H, additional, Homer, Nils, additional, Merriman, Barry, additional, Yu, Timothy W, additional, Flannery, Katherine C, additional, DeChene, Elizabeth T, additional, Towne, Meghan C, additional, Savage, Sarah K, additional, Price, Emily N, additional, Holm, Ingrid A, additional, Luquette, Lovelace J, additional, Lyon, Elaine, additional, Majzoub, Joseph, additional, Neupert, Peter, additional, McCallie Jr, David, additional, Szolovits, Peter, additional, Willard, Huntington F, additional, Mendelsohn, Nancy J, additional, Temme, Renee, additional, Finkel, Richard S, additional, Yum, Sabrina W, additional, Medne, Livija, additional, Sunyaev, Shamil R, additional, Adzhubey, Ivan, additional, Cassa, Christopher A, additional, de Bakker, Paul IW, additional, Duzkale, Hatice, additional, Dworzyński, Piotr, additional, Fairbrother, William, additional, Francioli, Laurent, additional, Funke, Birgit H, additional, Giovanni, Monica A, additional, Handsaker, Robert E, additional, Lage, Kasper, additional, Lebo, Matthew S, additional, Lek, Monkol, additional, Leshchiner, Ignaty, additional, MacArthur, Daniel G, additional, McLaughlin, Heather M, additional, Murray, Michael F, additional, Pers, Tune H, additional, Polak, Paz P, additional, Raychaudhuri, Soumya, additional, Rehm, Heidi L, additional, Soemedi, Rachel, additional, Stitziel, Nathan O, additional, Vestecka, Sara, additional, Supper, Jochen, additional, Gugenmus, Claudia, additional, Klocke, Bernward, additional, Hahn, Alexander, additional, Schubach, Max, additional, Menzel, Mortiz, additional, Biskup, Saskia, additional, Freisinger, Peter, additional, Deng, Mario, additional, Braun, Martin, additional, Perner, Sven, additional, Smith, Richard JH, additional, Andorf, Janeen L, additional, Huang, Jian, additional, Ryckman, Kelli, additional, Sheffield, Val C, additional, Stone, Edwin M, additional, Bair, Thomas, additional, Black-Ziegelbein, E, additional, Braun, Terry A, additional, Darbro, Benjamin, additional, DeLuca, Adam P, additional, Kolbe, Diana L, additional, Scheetz, Todd E, additional, Shearer, Aiden E, additional, Sompallae, Rama, additional, Wang, Kai, additional, Bassuk, Alexander G, additional, Edens, Erik, additional, Mathews, Katherine, additional, Moore, Steven A, additional, Shchelochkov, Oleg A, additional, Trapane, Pamela, additional, Bossler, Aaron, additional, Campbell, Colleen A, additional, Heusel, Jonathan W, additional, Kwitek, Anne, additional, Maga, Tara, additional, Panzer, Karin, additional, Wassink, Thomas, additional, Van Daele, Douglas, additional, Azaiez, Hela, additional, Booth, Kevin, additional, Meyer, Nic, additional, Segal, Michael M, additional, Williams, Marc S, additional, Tromp, Gerard, additional, White, Peter, additional, Corsmeier, Donald, additional, Fitzgerald-Butt, Sara, additional, Herman, Gail, additional, Lamb-Thrush, Devon, additional, McBride, Kim L, additional, Newsom, David, additional, Pierson, Christopher R, additional, Rakowsky, Alexander T, additional, Maver, Aleš, additional, Lovrečić, Luca, additional, Palandačić, Anja, additional, Peterlin, Borut, additional, Torkamani, Ali, additional, Wedell, Anna, additional, Huss, Mikael, additional, Alexeyenko, Andrey, additional, Lindvall, Jessica M, additional, Magnusson, Måns, additional, Nilsson, Daniel, additional, Stranneheim, Henrik, additional, Taylan, Fulya, additional, Gilissen, Christian, additional, Hoischen, Alexander, additional, van Bon, Bregje, additional, Yntema, Helger, additional, Nelen, Marcel, additional, Zhang, Weidong, additional, Sager, Jason, additional, Zhang, Lu, additional, Blair, Kathryn, additional, Kural, Deniz, additional, Cariaso, Michael, additional, Lennon, Greg G, additional, Javed, Asif, additional, Agrawal, Saloni, additional, Ng, Pauline C, additional, Sandhu, Komal S, additional, Krishna, Shuba, additional, Veeramachaneni, Vamsi, additional, Isakov, Ofer, additional, Halperin, Eran, additional, Friedman, Eitan, additional, Shomron, Noam, additional, Glusman, Gustavo, additional, Roach, Jared C, additional, Caballero, Juan, additional, Cox, Hannah C, additional, Mauldin, Denise, additional, Ament, Seth A, additional, Rowen, Lee, additional, Richards, Daniel R, additional, Lucas, F Anthony, additional, Gonzalez-Garay, Manuel L, additional, Caskey, C, additional, Bai, Yu, additional, Huang, Ying, additional, Fang, Fang, additional, Zhang, Yan, additional, Wang, Zhengyuan, additional, Barrera, Jorge, additional, Garcia-Lobo, Juan M, additional, González-Lamuño, Domingo, additional, Llorca, Javier, additional, Rodriguez, Maria C, additional, Varela, Ignacio, additional, Reese, Martin G, additional, De La Vega, Francisco M, additional, Kiruluta, Edward, additional, Cargill, Michele, additional, Hart, Reece K, additional, Sorenson, Jon M, additional, Lyon, Gholson J, additional, Stevenson, David A, additional, Bray, Bruce E, additional, Moore, Barry M, additional, Eilbeck, Karen, additional, Yandell, Mark, additional, Zhao, Hongyu, additional, Hou, Lin, additional, Chen, Xiaowei, additional, Yan, Xiting, additional, Chen, Mengjie, additional, Li, Cong, additional, Yang, Can, additional, Gunel, Murat, additional, Li, Peining, additional, Kong, Yong, additional, Alexander, Austin C, additional, Albertyn, Zayed I, additional, Boycott, Kym M, additional, Bulman, Dennis E, additional, Gordon, Paul MK, additional, Innes, A, additional, Knoppers, Bartha M, additional, Majewski, Jacek, additional, Marshall, Christian R, additional, Parboosingh, Jillian S, additional, Sawyer, Sarah L, additional, Samuels, Mark E, additional, Schwartzentruber, Jeremy, additional, Kohane, Isaac S, additional, and Margulies, David M, additional

Published
2014
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240. Technology platform development for targeted plasma metabolites in human heart failure

Author

Chan, CY, Chan, CY, Khan, Anjum A, Choi, JH, Ng, CM, Cadeiras, Martin, Deng, Mario, Ping, Peipei, Chan, CY, Chan, CY, Khan, Anjum A, Choi, JH, Ng, CM, Cadeiras, Martin, Deng, Mario, and Ping, Peipei

Abstract

Background Heart failure is a multifactorial disease associated with staggeringly high morbidity and motility. Recently, alterations of multiple metabolites have been implicated in heart failure; however, the lack of an effective technology platform to assess these metabolites has limited our understanding on how they contribute to this disease phenotype. We have successfully developed a new workflow combining specific sample preparation with tandem mass spectrometry that enables us to extract most of the targeted metabolites. 19 metabolites were chosen ascribing to their biological relevance to heart failure, including extracellular matrix remodeling, inflammation, insulin resistance, renal dysfunction, and cardioprotection against ischemic injury. Results In this report, we systematically engineered, optimized and refined a protocol applicable to human plasma samples; this study contributes to the methodology development with respect to deproteinization, incubation, reconstitution, and detection with mass spectrometry. The deproteinization step was optimized with 20% methanol/ethanol at a plasma:solvent ratio of 1:3. Subsequently, an incubation step was implemented which remarkably enhanced the metabolite signals and the number of metabolite peaks detected by mass spectrometry in both positive and negative modes. With respect to the step of reconstitution, 0.1% formic acid was designated as the reconstitution solvent vs. 6.5 mM ammonium bicarbonate, based on the comparable number of metabolite peaks detected in both solvents, and yet the signal detected in the former was higher. By adapting this finalized protocol, we were able to retrieve 13 out of 19 targeted metabolites from human plasma. Conclusions We have successfully devised a simple albeit effective workflow for the targeted plasma metabolites relevant to human heart failure. This will be employed in tandem with high throughput liquid chromatography mass spectrometry platform to validate and chara

Published
2013

241. Understanding the Correlation Between DSA, Complement Activation, and Antibody-Mediated Rejection in Heart Transplant Recipients

Author

Zhang, Qiuheng, Hickey, Michelle, Drogalis-Kim, Diana, Zheng, Ying, Gjertson, David, Cadeiras, Martin, Khuu, Tam, Baas, Arnold S., Depasquale, Eugene C., Halnon, Nancy J., Perens, Gregory, Alejos, Juan, Cruz, Daniel, Ali, Nsair, Shemin, Richard, Kwon, Murray, Fishbein, Michael C., Ardehali, Abbas, Deng, Mario, and Reed, Elaine F.

Abstract

In 176 adult and pediatric heart transplant recipients, the authors report on the association of preformed and de novo DSA (especially if they are C3d+) with a higher risk of antibody-mediated rejection.

Published
2018
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246. Somatic copy number alterations by whole‐exome sequencing implicatesYWHAZandPTK2in castration‐resistant prostate cancer

Author

Menon, Roopika, primary, Deng, Mario, additional, Rüenauver, Kerstin, additional, Queisser, Angela, additional, Pfeifer, Martin, additional, Offermann, Anne, additional, Boehm, Diana, additional, Vogel, Wenzel, additional, Scheble, Veit, additional, Fend, Falko, additional, Kristiansen, Glen, additional, Wernert, Nicolas, additional, Oberbeckmann, Nicole, additional, Biskup, Saskia, additional, Rubin, Mark A, additional, Adler, David, additional, and Perner, Sven, additional

Published
2013
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250. Preoperative Assessment of High-Risk Candidates to Predict Survival After Heart Transplantation

Author

Schulze, P. Christian, primary, Jiang, Jeffrey, additional, Yang, Jonathan, additional, Cheema, Faisal H., additional, Schaeffle, Kenneth, additional, Kato, Tomoko S., additional, Farr, Maryjane, additional, Restaino, Susan, additional, Deng, Mario, additional, Maurer, Mathew, additional, Horn, Evelyn, additional, Latif, Farhana, additional, Colombo, Paolo C., additional, Jorde, Ulrich, additional, Uriel, Nir, additional, Haythe, Jennifer, additional, Bijou, Rachel, additional, Drusin, Ron, additional, Lee, Sun Hi, additional, Takayama, Hiroo, additional, Naka, Yoshifumi, additional, and Mancini, Donna M., additional

Published
2013
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