المؤلفون: Nathaniel R. Smilowitz, MacIntosh Cornwell, Erik J. Offerman, Caron B. Rockman, Svati H. Shah, Jonathan D. Newman, Kelly Ruggles, Deepak Voora, Jeffrey S. Berger

المصدر: Scientific Reports, Vol 12, Iss 1, Pp 1-12 (2022)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Myocardial injury after non-cardiac surgery (MINS) is common. We investigated the incidence and outcomes of MINS, and mechanistic underpinnings using pre-operative whole blood gene expression profiling in a prospective cohort study of individuals undergoing lower extremity revascularization (LER) for peripheral artery disease (PAD). Major adverse cardiovascular and limb events (MACLE) were defined as a composite of death, myocardial infarction, stroke, major lower extremity amputation or reoperation. Among 226 participants undergoing LER, MINS occurred in 53 (23.5%). Patients with MINS had a greater incidence of major adverse cardiovascular events (49.1% vs. 22.0%, adjusted HR 1.87, 95% CI 1.07–3.26) and MACLE (67.9% vs. 44.5%; adjusted HR 1.66, 95% CI 1.08–2.55) at median 20-month follow-up. Pre-operative whole blood transcriptome profiling of a nested matched MINS case–control cohort (n = 41) identified upregulation of pathways related to platelet alpha granules and coagulation in patients who subsequently developed MINS. Thrombospondin 1 (THBS1) mRNA expression was 60% higher at baseline in patients who later developed MINS, and was independently associated with long-term cardiovascular events in the Duke Catheterization Genetics biorepository cohort. In conclusion, pre-operative THBS1 mRNA expression is higher in patients who subsequently develop MINS and is associated with incident cardiovascular events. Pathways related to platelet activity and coagulation associated with MINS provide novel insights into mechanisms of myocardial injury.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2045-2322

URL الوصول: https://doaj.org/article/22f0d535d13a4dcba54163ced36bd594

المؤلفون: Jill Buyon, Peter Izmirly, Gregg J Silverman, Doua F Azzouz, Kelly Ruggles, Macintosh Cornwell

المصدر: Lupus Science and Medicine, Vol 9, Iss Suppl 3 (2022)

مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2053-8790

URL الوصول: https://doaj.org/article/fb219ff5477947609011b793363ba5fb

المؤلفون: Priscillia Lhoumaud, Gunjan Sethia, Franco Izzo, Theodore Sakellaropoulos, Valentina Snetkova, Simon Vidal, Sana Badri, Macintosh Cornwell, Dafne Campigli Di Giammartino, Kyu-Tae Kim, Effie Apostolou, Matthias Stadtfeld, Dan Avi Landau, Jane Skok

المصدر: Genome Biology, Vol 20, Iss 1, Pp 1-12 (2019)

مصطلحات موضوعية: DNA methylation, Chromatin accessibility, ChIP, ATAC, CTCF, KLF4, Biology (General), QH301-705.5, Genetics, QH426-470

الوصف: Abstract Activation of regulatory elements is thought to be inversely correlated with DNA methylation levels. However, it is difficult to determine whether DNA methylation is compatible with chromatin accessibility or transcription factor (TF) binding if assays are performed separately. We developed a fast, low-input, low sequencing depth method, EpiMethylTag, that combines ATAC-seq or ChIP-seq (M-ATAC or M-ChIP) with bisulfite conversion, to simultaneously examine accessibility/TF binding and methylation on the same DNA. Here we demonstrate that EpiMethylTag can be used to study the functional interplay between chromatin accessibility and TF binding (CTCF and KLF4) at methylated sites.

وصف الملف: electronic resource

Relation: http://link.springer.com/article/10.1186/s13059-019-1853-6; https://doaj.org/toc/1474-760X

URL الوصول: https://doaj.org/article/05d80c0806d0468d85038fa65c963014

المؤلفون: Priscillia Lhoumaud, Sana Badri, Javier Rodriguez-Hernaez, Theodore Sakellaropoulos, Gunjan Sethia, Andreas Kloetgen, MacIntosh Cornwell, Sourya Bhattacharyya, Ferhat Ay, Richard Bonneau, Aristotelis Tsirigos, Jane A. Skok

المصدر: Nature Communications, Vol 10, Iss 1, Pp 1-18 (2019)

مصطلحات موضوعية: Science

الوصف: In multiple myeloma, a 4;14 translocation induces overexpression of histone methyltransferase NSD2, resulting in expansion of H3K36me2 and shrinkage of H3K27me3 domains. Here the authors find that CTCF, H3K27ac and gene expression changes cluster within a subset of insulated domains implicating 3D chromosome organization as a key factor in the NSD2-mediated phenotype.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2041-1723

URL الوصول: https://doaj.org/article/a9714ab2ecf84d2fb21b384d6ebd3d76

المؤلفون: MacIntosh Cornwell, Mahesh Vangala, Len Taing, Zachary Herbert, Johannes Köster, Bo Li, Hanfei Sun, Taiwen Li, Jian Zhang, Xintao Qiu, Matthew Pun, Rinath Jeselsohn, Myles Brown, X. Shirley Liu, Henry W. Long

المصدر: BMC Bioinformatics, Vol 19, Iss 1, Pp 1-14 (2018)

مصطلحات موضوعية: RNA-seq, Analysis, Pipeline, Snakemake, Gene fusion, Immunological infiltrate, Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5

الوصف: Abstract Background RNA sequencing has become a ubiquitous technology used throughout life sciences as an effective method of measuring RNA abundance quantitatively in tissues and cells. The increase in use of RNA-seq technology has led to the continuous development of new tools for every step of analysis from alignment to downstream pathway analysis. However, effectively using these analysis tools in a scalable and reproducible way can be challenging, especially for non-experts. Results Using the workflow management system Snakemake we have developed a user friendly, fast, efficient, and comprehensive pipeline for RNA-seq analysis. VIPER (Visualization Pipeline for RNA-seq analysis) is an analysis workflow that combines some of the most popular tools to take RNA-seq analysis from raw sequencing data, through alignment and quality control, into downstream differential expression and pathway analysis. VIPER has been created in a modular fashion to allow for the rapid incorporation of new tools to expand the capabilities. This capacity has already been exploited to include very recently developed tools that explore immune infiltrate and T-cell CDR (Complementarity-Determining Regions) reconstruction abilities. The pipeline has been conveniently packaged such that minimal computational skills are required to download and install the dozens of software packages that VIPER uses. Conclusions VIPER is a comprehensive solution that performs most standard RNA-seq analyses quickly and effectively with a built-in capacity for customization and expansion.

وصف الملف: electronic resource

Relation: http://link.springer.com/article/10.1186/s12859-018-2139-9; https://doaj.org/toc/1471-2105

URL الوصول: https://doaj.org/article/05f5ce1145074e0bbe0ea6794782fc82

المؤلفون: Hanane El Bannoudi, MacIntosh Cornwell, Elliot Luttrell‐Williams, Alexis Engel, Christina Rolling, Tessa J. Barrett, Peter Izmirly, H. Michael Belmont, Kelly Ruggles, Robert Clancy, Jill Buyon, Jeffrey S. Berger

المصدر: Arthritis & Rheumatology. 75:711-722

مصطلحات موضوعية: Rheumatology, Immunology, Immunology and Allergy

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::8d6a3a7b0fc8760c8bde6408fa2144fa
https://doi.org/10.1002/art.42382

المؤلفون: Agostina Nardone, Xintao Qiu, Sandor Spisak, Zsuzsanna Nagy, Ariel Feiglin, Avery Feit, Gabriela Cohen Feit, Yingtian Xie, Alba Font-Tello, Cristina Guarducci, Francisco Hermida-Prado, Sudeepa Syamala, Klothilda Lim, Miguel Munoz Gomez, Matthew Pun, MacIntosh Cornwell, Weihan Liu, Aysegul Ors, Hisham Mohammed, Paloma Cejas, Jane B. Brock, Matthew L. Freedman, Eric P. Winer, Xiaoyong Fu, Rachel Schiff, Henry W. Long, Otto Metzger Filho, Rinath Jeselsohn

المصدر: Cancer Res

مصطلحات موضوعية: Carcinoma, Lobular, Tamoxifen, Cancer Research, Receptors, Estrogen, Oncology, Drug Resistance, Neoplasm, Carcinoma, Ductal, Breast, Humans, Breast Neoplasms, Female, Prognosis, Chromatin, Article

الوصف: Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor–positive. Yet, ILC is relatively resistant to tamoxifen and associated with inferior long-term outcomes compared with invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. A comprehensive analysis of the epigenome of ILC in preclinical models and clinical samples showed that, compared with IDC, ILC harbored a distinct chromatin state linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This resulted in an ILC-unique FOXA1–estrogen receptor (ER) axis that promoted the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1–ER axis led to retained ER chromatin binding after tamoxifen treatment, which facilitated tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the autoinduction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC. In summary, ILC is characterized by a unique chromatin state and FOXA1–ER axis that is associated with tumor progression, offering a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC in order to optimize treatments in this breast cancer subtype. Significance: A unique FOXA1–ER axis in invasive lobular breast cancer promotes disease progression and tamoxifen resistance, highlighting a potential therapeutic avenue for clinical investigations dedicated to this disease. See related commentary by Blawski and Toska, p. 3668

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a0ba56c1184a5cedf045c241e017be95
https://doi.org/10.1158/0008-5472.can-21-3186

المؤلفون: Rinath Jeselsohn, Otto Metzger Filho, Henry W. Long, Rachel Schiff, Xiaoyong Fu, Eric P. Winer, Matthew L. Freedman, Jane B. Brock, Paloma Cejas, Hisham Mohammed, Aysegul Ors, Weihan Liu, MacIntosh Cornwell, Matthew Pun, Miguel Munoz Gomez, Klothilda Lim, Sudeepa Syamala, Francisco Hermida-Prado, Cristina Guarducci, Alba Font-Tello, Yingtian Xie, Gabriela Cohen Feit, Avery Feit, Ariel Feiglin, Zsuzsanna Nagy, Sandor Spisak, Xintao Qiu, Agostina Nardone

الوصف: Supplementary Table from A Distinct Chromatin State Drives Therapeutic Resistance in Invasive Lobular Breast Cancer

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::644d4a0422e250cec5f0ba2f7557a6cc
https://doi.org/10.1158/0008-5472.22432398

المؤلفون: Rinath Jeselsohn, Otto Metzger Filho, Henry W. Long, Rachel Schiff, Xiaoyong Fu, Eric P. Winer, Matthew L. Freedman, Jane B. Brock, Paloma Cejas, Hisham Mohammed, Aysegul Ors, Weihan Liu, MacIntosh Cornwell, Matthew Pun, Miguel Munoz Gomez, Klothilda Lim, Sudeepa Syamala, Francisco Hermida-Prado, Cristina Guarducci, Alba Font-Tello, Yingtian Xie, Gabriela Cohen Feit, Avery Feit, Ariel Feiglin, Zsuzsanna Nagy, Sandor Spisak, Xintao Qiu, Agostina Nardone

الوصف: Supplementary Figure from A Distinct Chromatin State Drives Therapeutic Resistance in Invasive Lobular Breast Cancer

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f3f88a0fff75196b0b08116e20f8d54
https://doi.org/10.1158/0008-5472.22432410.v1

المؤلفون: Rinath Jeselsohn, Otto Metzger Filho, Henry W. Long, Rachel Schiff, Xiaoyong Fu, Eric P. Winer, Matthew L. Freedman, Jane B. Brock, Paloma Cejas, Hisham Mohammed, Aysegul Ors, Weihan Liu, MacIntosh Cornwell, Matthew Pun, Miguel Munoz Gomez, Klothilda Lim, Sudeepa Syamala, Francisco Hermida-Prado, Cristina Guarducci, Alba Font-Tello, Yingtian Xie, Gabriela Cohen Feit, Avery Feit, Ariel Feiglin, Zsuzsanna Nagy, Sandor Spisak, Xintao Qiu, Agostina Nardone

الوصف: Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor–positive. Yet, ILC is relatively resistant to tamoxifen and associated with inferior long-term outcomes compared with invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. A comprehensive analysis of the epigenome of ILC in preclinical models and clinical samples showed that, compared with IDC, ILC harbored a distinct chromatin state linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This resulted in an ILC-unique FOXA1–estrogen receptor (ER) axis that promoted the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1–ER axis led to retained ER chromatin binding after tamoxifen treatment, which facilitated tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the autoinduction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC. In summary, ILC is characterized by a unique chromatin state and FOXA1–ER axis that is associated with tumor progression, offering a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC in order to optimize treatments in this breast cancer subtype.Significance:A unique FOXA1–ER axis in invasive lobular breast cancer promotes disease progression and tamoxifen resistance, highlighting a potential therapeutic avenue for clinical investigations dedicated to this disease.See related commentary by Blawski and Toska, p. 3668

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::b9f4303f8d7b93b042806e9b013252f7
https://doi.org/10.1158/0008-5472.c.6514143.v1