A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding

Publication Date:
2018-12-14
Publisher:
American Society of Hematology (ASH)
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
Medicine
Keywords:
Thrombosis and Hemostasis, e-Blood
Published by:
http://www.hematology.org/
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autor Baaten, C. C. F. M. J., Meacham, S., de Witt, S. M., Feijge, M. A. H., Adams, D. J., Akkerman, J.-W. N., Cosemans, J. M. E. M., Grassi, L., Jupe, S., Kostadima, M., Mattheij, N. J. A., Prins, M. H., Ramirez-Solis, R., Soehnlein, O., Swieringa, F., Weber, C., White, J. K., Ouwehand, W. H., Heemskerk, J. W. M.
beschreibung Antithrombotic therapies reduce cardiovascular diseases by preventing arterial thrombosis and thromboembolism, but at expense of increased bleeding risks. Arterial thrombosis studies using genetically modified mice have been invaluable for identification of new molecular targets. Because of low sample sizes and heterogeneity in approaches or methodologies, a formal meta-analysis to compare studies of mice with single-gene defects encountered major limitations. To overcome these, we developed a novel synthesis approach to quantitatively scale 1514 published studies of arterial thrombus formation (in vivo and in vitro), thromboembolism, and tail-bleeding of genetically modified mice. Using a newly defined consistency parameter (CP), indicating the strength of published data, comparisons were made of 431 mouse genes, of which 17 consistently contributed to thrombus formation without affecting hemostasis. Ranking analysis indicated high correlations between collagen-dependent thrombosis models in vivo (FeCl 3 injury or ligation/compression) and in vitro. Integration of scores and CP values resulted in a network of protein interactions in thrombosis and hemostasis (PITH), which was combined with databases of genetically linked human bleeding and thrombotic disorders. The network contained 2946 nodes linked to modifying genes of thrombus formation, mostly with expression in megakaryocytes. Reactome pathway analysis and network characteristics revealed multiple novel genes with potential contribution to thrombosis/hemostasis. Studies with additional knockout mice revealed that 4 of 8 ( Apoe , Fpr2 , Ifnar1 , Vps13a ) new genes were modifying in thrombus formation. The PITH network further: (i) revealed a high similarity of murine and human hemostatic and thrombotic processes and (ii) identified multiple new candidate proteins regulating these processes.
citation_standardnr 6369100
datenlieferant ipn_articles
feed_id 310
feed_publisher American Society of Hematology (ASH)
feed_publisher_url http://www.hematology.org/
insertion_date 2018-12-14
journaleissn 1528-0020
journalissn 0006-4971
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Society of Hematology (ASH)
quelle Blood
relation http://www.bloodjournal.org/cgi/content/short/132/24/e35?rss=1
schlagwort Thrombosis and Hemostasis, e-Blood
search_space articles
shingle_author_1 Baaten, C. C. F. M. J., Meacham, S., de Witt, S. M., Feijge, M. A. H., Adams, D. J., Akkerman, J.-W. N., Cosemans, J. M. E. M., Grassi, L., Jupe, S., Kostadima, M., Mattheij, N. J. A., Prins, M. H., Ramirez-Solis, R., Soehnlein, O., Swieringa, F., Weber, C., White, J. K., Ouwehand, W. H., Heemskerk, J. W. M.
shingle_author_2 Baaten, C. C. F. M. J., Meacham, S., de Witt, S. M., Feijge, M. A. H., Adams, D. J., Akkerman, J.-W. N., Cosemans, J. M. E. M., Grassi, L., Jupe, S., Kostadima, M., Mattheij, N. J. A., Prins, M. H., Ramirez-Solis, R., Soehnlein, O., Swieringa, F., Weber, C., White, J. K., Ouwehand, W. H., Heemskerk, J. W. M.
shingle_author_3 Baaten, C. C. F. M. J., Meacham, S., de Witt, S. M., Feijge, M. A. H., Adams, D. J., Akkerman, J.-W. N., Cosemans, J. M. E. M., Grassi, L., Jupe, S., Kostadima, M., Mattheij, N. J. A., Prins, M. H., Ramirez-Solis, R., Soehnlein, O., Swieringa, F., Weber, C., White, J. K., Ouwehand, W. H., Heemskerk, J. W. M.
shingle_author_4 Baaten, C. C. F. M. J., Meacham, S., de Witt, S. M., Feijge, M. A. H., Adams, D. J., Akkerman, J.-W. N., Cosemans, J. M. E. M., Grassi, L., Jupe, S., Kostadima, M., Mattheij, N. J. A., Prins, M. H., Ramirez-Solis, R., Soehnlein, O., Swieringa, F., Weber, C., White, J. K., Ouwehand, W. H., Heemskerk, J. W. M.
shingle_catch_all_1 A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding
Thrombosis and Hemostasis, e-Blood
Antithrombotic therapies reduce cardiovascular diseases by preventing arterial thrombosis and thromboembolism, but at expense of increased bleeding risks. Arterial thrombosis studies using genetically modified mice have been invaluable for identification of new molecular targets. Because of low sample sizes and heterogeneity in approaches or methodologies, a formal meta-analysis to compare studies of mice with single-gene defects encountered major limitations. To overcome these, we developed a novel synthesis approach to quantitatively scale 1514 published studies of arterial thrombus formation (in vivo and in vitro), thromboembolism, and tail-bleeding of genetically modified mice. Using a newly defined consistency parameter (CP), indicating the strength of published data, comparisons were made of 431 mouse genes, of which 17 consistently contributed to thrombus formation without affecting hemostasis. Ranking analysis indicated high correlations between collagen-dependent thrombosis models in vivo (FeCl 3 injury or ligation/compression) and in vitro. Integration of scores and CP values resulted in a network of protein interactions in thrombosis and hemostasis (PITH), which was combined with databases of genetically linked human bleeding and thrombotic disorders. The network contained 2946 nodes linked to modifying genes of thrombus formation, mostly with expression in megakaryocytes. Reactome pathway analysis and network characteristics revealed multiple novel genes with potential contribution to thrombosis/hemostasis. Studies with additional knockout mice revealed that 4 of 8 ( Apoe , Fpr2 , Ifnar1 , Vps13a ) new genes were modifying in thrombus formation. The PITH network further: (i) revealed a high similarity of murine and human hemostatic and thrombotic processes and (ii) identified multiple new candidate proteins regulating these processes.
Baaten, C. C. F. M. J., Meacham, S., de Witt, S. M., Feijge, M. A. H., Adams, D. J., Akkerman, J.-W. N., Cosemans, J. M. E. M., Grassi, L., Jupe, S., Kostadima, M., Mattheij, N. J. A., Prins, M. H., Ramirez-Solis, R., Soehnlein, O., Swieringa, F., Weber, C., White, J. K., Ouwehand, W. H., Heemskerk, J. W. M.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_2 A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding
Thrombosis and Hemostasis, e-Blood
Antithrombotic therapies reduce cardiovascular diseases by preventing arterial thrombosis and thromboembolism, but at expense of increased bleeding risks. Arterial thrombosis studies using genetically modified mice have been invaluable for identification of new molecular targets. Because of low sample sizes and heterogeneity in approaches or methodologies, a formal meta-analysis to compare studies of mice with single-gene defects encountered major limitations. To overcome these, we developed a novel synthesis approach to quantitatively scale 1514 published studies of arterial thrombus formation (in vivo and in vitro), thromboembolism, and tail-bleeding of genetically modified mice. Using a newly defined consistency parameter (CP), indicating the strength of published data, comparisons were made of 431 mouse genes, of which 17 consistently contributed to thrombus formation without affecting hemostasis. Ranking analysis indicated high correlations between collagen-dependent thrombosis models in vivo (FeCl 3 injury or ligation/compression) and in vitro. Integration of scores and CP values resulted in a network of protein interactions in thrombosis and hemostasis (PITH), which was combined with databases of genetically linked human bleeding and thrombotic disorders. The network contained 2946 nodes linked to modifying genes of thrombus formation, mostly with expression in megakaryocytes. Reactome pathway analysis and network characteristics revealed multiple novel genes with potential contribution to thrombosis/hemostasis. Studies with additional knockout mice revealed that 4 of 8 ( Apoe , Fpr2 , Ifnar1 , Vps13a ) new genes were modifying in thrombus formation. The PITH network further: (i) revealed a high similarity of murine and human hemostatic and thrombotic processes and (ii) identified multiple new candidate proteins regulating these processes.
Baaten, C. C. F. M. J., Meacham, S., de Witt, S. M., Feijge, M. A. H., Adams, D. J., Akkerman, J.-W. N., Cosemans, J. M. E. M., Grassi, L., Jupe, S., Kostadima, M., Mattheij, N. J. A., Prins, M. H., Ramirez-Solis, R., Soehnlein, O., Swieringa, F., Weber, C., White, J. K., Ouwehand, W. H., Heemskerk, J. W. M.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_3 A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding
Thrombosis and Hemostasis, e-Blood
Antithrombotic therapies reduce cardiovascular diseases by preventing arterial thrombosis and thromboembolism, but at expense of increased bleeding risks. Arterial thrombosis studies using genetically modified mice have been invaluable for identification of new molecular targets. Because of low sample sizes and heterogeneity in approaches or methodologies, a formal meta-analysis to compare studies of mice with single-gene defects encountered major limitations. To overcome these, we developed a novel synthesis approach to quantitatively scale 1514 published studies of arterial thrombus formation (in vivo and in vitro), thromboembolism, and tail-bleeding of genetically modified mice. Using a newly defined consistency parameter (CP), indicating the strength of published data, comparisons were made of 431 mouse genes, of which 17 consistently contributed to thrombus formation without affecting hemostasis. Ranking analysis indicated high correlations between collagen-dependent thrombosis models in vivo (FeCl 3 injury or ligation/compression) and in vitro. Integration of scores and CP values resulted in a network of protein interactions in thrombosis and hemostasis (PITH), which was combined with databases of genetically linked human bleeding and thrombotic disorders. The network contained 2946 nodes linked to modifying genes of thrombus formation, mostly with expression in megakaryocytes. Reactome pathway analysis and network characteristics revealed multiple novel genes with potential contribution to thrombosis/hemostasis. Studies with additional knockout mice revealed that 4 of 8 ( Apoe , Fpr2 , Ifnar1 , Vps13a ) new genes were modifying in thrombus formation. The PITH network further: (i) revealed a high similarity of murine and human hemostatic and thrombotic processes and (ii) identified multiple new candidate proteins regulating these processes.
Baaten, C. C. F. M. J., Meacham, S., de Witt, S. M., Feijge, M. A. H., Adams, D. J., Akkerman, J.-W. N., Cosemans, J. M. E. M., Grassi, L., Jupe, S., Kostadima, M., Mattheij, N. J. A., Prins, M. H., Ramirez-Solis, R., Soehnlein, O., Swieringa, F., Weber, C., White, J. K., Ouwehand, W. H., Heemskerk, J. W. M.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_4 A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding
Thrombosis and Hemostasis, e-Blood
Antithrombotic therapies reduce cardiovascular diseases by preventing arterial thrombosis and thromboembolism, but at expense of increased bleeding risks. Arterial thrombosis studies using genetically modified mice have been invaluable for identification of new molecular targets. Because of low sample sizes and heterogeneity in approaches or methodologies, a formal meta-analysis to compare studies of mice with single-gene defects encountered major limitations. To overcome these, we developed a novel synthesis approach to quantitatively scale 1514 published studies of arterial thrombus formation (in vivo and in vitro), thromboembolism, and tail-bleeding of genetically modified mice. Using a newly defined consistency parameter (CP), indicating the strength of published data, comparisons were made of 431 mouse genes, of which 17 consistently contributed to thrombus formation without affecting hemostasis. Ranking analysis indicated high correlations between collagen-dependent thrombosis models in vivo (FeCl 3 injury or ligation/compression) and in vitro. Integration of scores and CP values resulted in a network of protein interactions in thrombosis and hemostasis (PITH), which was combined with databases of genetically linked human bleeding and thrombotic disorders. The network contained 2946 nodes linked to modifying genes of thrombus formation, mostly with expression in megakaryocytes. Reactome pathway analysis and network characteristics revealed multiple novel genes with potential contribution to thrombosis/hemostasis. Studies with additional knockout mice revealed that 4 of 8 ( Apoe , Fpr2 , Ifnar1 , Vps13a ) new genes were modifying in thrombus formation. The PITH network further: (i) revealed a high similarity of murine and human hemostatic and thrombotic processes and (ii) identified multiple new candidate proteins regulating these processes.
Baaten, C. C. F. M. J., Meacham, S., de Witt, S. M., Feijge, M. A. H., Adams, D. J., Akkerman, J.-W. N., Cosemans, J. M. E. M., Grassi, L., Jupe, S., Kostadima, M., Mattheij, N. J. A., Prins, M. H., Ramirez-Solis, R., Soehnlein, O., Swieringa, F., Weber, C., White, J. K., Ouwehand, W. H., Heemskerk, J. W. M.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_title_1 A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding
shingle_title_2 A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding
shingle_title_3 A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding
shingle_title_4 A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding
timestamp 2025-07-31T23:47:49.187Z
titel A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding
titel_suche A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding
topic W
WW-YZ
uid ipn_articles_6369100