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  1. AU="Halpert, Richard"
  2. AU="Alkorta, Ibon"
  3. AU="Kwon, Kyungmi"
  4. AU="Bernardo Salasnich"
  5. AU="Hassan, Zurina"
  6. AU="Belarbi, M"
  7. AU="Rout, Ranjeet K"
  8. AU="Moreira, Catarina"
  9. AU=Warn-Cramer Bonnie J
  10. AU="Morral, Núria"
  11. AU="Silman, Miles R."
  12. AU="Palfi Salavat, Mădălina-Casiana"
  13. AU="Mohamed, Eid"
  14. AU="Hudson, Lance"
  15. AU="Imane Mihoub" AU="Imane Mihoub"
  16. AU="D. M. Wuchenich"

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  1. Artikel ; Online: Automated optimized parameters for T-distributed stochastic neighbor embedding improve visualization and analysis of large datasets.

    Belkina, Anna C / Ciccolella, Christopher O / Anno, Rina / Halpert, Richard / Spidlen, Josef / Snyder-Cappione, Jennifer E

    Nature communications

    2019  Band 10, Heft 1, Seite(n) 5415

    Abstract: Accurate and comprehensive extraction of information from high-dimensional single cell datasets necessitates faithful visualizations to assess biological populations. A state-of-the-art algorithm for non-linear dimension reduction, t-SNE, requires ... ...

    Abstract Accurate and comprehensive extraction of information from high-dimensional single cell datasets necessitates faithful visualizations to assess biological populations. A state-of-the-art algorithm for non-linear dimension reduction, t-SNE, requires multiple heuristics and fails to produce clear representations of datasets when millions of cells are projected. We develop opt-SNE, an automated toolkit for t-SNE parameter selection that utilizes Kullback-Leibler divergence evaluation in real time to tailor the early exaggeration and overall number of gradient descent iterations in a dataset-specific manner. The precise calibration of early exaggeration together with opt-SNE adjustment of gradient descent learning rate dramatically improves computation time and enables high-quality visualization of large cytometry and transcriptomics datasets, overcoming limitations of analysis tools with hard-coded parameters that often produce poorly resolved or misleading maps of fluorescent and mass cytometry data. In summary, opt-SNE enables superior data resolution in t-SNE space and thereby more accurate data interpretation.
    Mesh-Begriff(e) Algorithms ; Animals ; Automation ; Computational Biology ; Data Visualization ; Datasets as Topic ; Flow Cytometry ; Gene Expression Profiling ; Humans ; Machine Learning ; Mice ; Nonlinear Dynamics ; Principal Component Analysis
    Sprache Englisch
    Erscheinungsdatum 2019-11-28
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-019-13055-y
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: AutoSpill is a principled framework that simplifies the analysis of multichromatic flow cytometry data.

    Roca, Carlos P / Burton, Oliver T / Gergelits, Václav / Prezzemolo, Teresa / Whyte, Carly E / Halpert, Richard / Kreft, Łukasz / Collier, James / Botzki, Alexander / Spidlen, Josef / Humblet-Baron, Stéphanie / Liston, Adrian

    Nature communications

    2021  Band 12, Heft 1, Seite(n) 2890

    Abstract: Compensating in flow cytometry is an unavoidable challenge in the data analysis of fluorescence-based flow cytometry. Even the advent of spectral cytometry cannot circumvent the spillover problem, with spectral unmixing an intrinsic part of such systems. ...

    Abstract Compensating in flow cytometry is an unavoidable challenge in the data analysis of fluorescence-based flow cytometry. Even the advent of spectral cytometry cannot circumvent the spillover problem, with spectral unmixing an intrinsic part of such systems. The calculation of spillover coefficients from single-color controls has remained essentially unchanged since its inception, and is increasingly limited in its ability to deal with high-parameter flow cytometry. Here, we present AutoSpill, an alternative method for calculating spillover coefficients. The approach combines automated gating of cells, calculation of an initial spillover matrix based on robust linear regression, and iterative refinement to reduce error. Moreover, autofluorescence can be compensated out, by processing it as an endogenous dye in an unstained control. AutoSpill uses single-color controls and is compatible with common flow cytometry software. AutoSpill allows simpler and more robust workflows, while reducing the magnitude of compensation errors in high-parameter flow cytometry.
    Sprache Englisch
    Erscheinungsdatum 2021-05-17
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-23126-8
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease.

    Bouquet, Jerome / Soloski, Mark J / Swei, Andrea / Cheadle, Chris / Federman, Scot / Billaud, Jean-Noel / Rebman, Alison W / Kabre, Beniwende / Halpert, Richard / Boorgula, Meher / Aucott, John N / Chiu, Charles Y

    mBio

    2016  Band 7, Heft 1, Seite(n) e00100–16

    Abstract: Unlabelled: Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights ... ...

    Abstract Unlabelled: Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the "window period" of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets.
    Importance: Lyme disease is the most common tick-borne infection in the United States, and some patients report lingering symptoms lasting months to years despite antibiotic treatment. To better understand the role of the human host response in acute Lyme disease and the development of post-treatment symptoms, we conducted the first longitudinal gene expression (transcriptome) study of patients enrolled at the time of diagnosis and followed up for up to 6 months after treatment. Importantly, we found that the gene expression signature of early Lyme disease is distinct from that of other acute infectious diseases and persists for at least 3 weeks following infection. This study also uncovered multiple previously undescribed pathways and genes that may be useful in the future as human host biomarkers for diagnosis and that constitute potential targets for the development of new therapies.
    Mesh-Begriff(e) Adult ; Animals ; Biomarkers/blood ; Borrelia burgdorferi/physiology ; Female ; Gene Expression Profiling/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Lyme Disease/diagnosis ; Lyme Disease/drug therapy ; Lyme Disease/genetics ; Lyme Disease/microbiology ; Male ; Metabolic Networks and Pathways/genetics ; Middle Aged ; Transcriptome ; United States
    Chemische Substanzen Biomarkers
    Sprache Englisch
    Erscheinungsdatum 2016-02-12
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.00100-16
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Interferon regulatory factor 1 is an independent predictor of platinum resistance and survival in high-grade serous ovarian carcinoma.

    Cohen, Samantha / Mosig, Rebecca / Moshier, Erin / Pereira, Elena / Rahaman, Jamal / Prasad-Hayes, Monica / Halpert, Richard / Billaud, Jean-Noel / Dottino, Peter / Martignetti, John A

    Gynecologic oncology

    2014  Band 134, Heft 3, Seite(n) 591–598

    Abstract: Objective: High-grade serous ovarian cancer (HGSOC) that is resistant to platinum-based chemotherapy has a particularly poor prognosis. Response to platinum has both prognostic survival value and dictates secondary treatment strategies. Using ... ...

    Abstract Objective: High-grade serous ovarian cancer (HGSOC) that is resistant to platinum-based chemotherapy has a particularly poor prognosis. Response to platinum has both prognostic survival value and dictates secondary treatment strategies. Using transcriptome analysis, we sought to identify differentially expressed genes/pathways based on a tumor's platinum response for discovering novel predictive biomarkers.
    Methods: Seven primary HGSOC tumor samples, representing two extremes of platinum sensitivity/timing of disease recurrence, were analyzed by RNA-Seq, Ingenuity Pathways Analysis (IPA) and Upstream Regulator Analysis (URA), and used to explore differentially expressed genes and prevalent molecular and cellular processes. Progression-free and overall survival (PFS, OS) was estimated using the Kaplan-Meier method in two different sample sets including GEO and TCGA data sets.
    Results: IPA and URA highlighted an IRF1-driven transcriptional program (P=0.0017; z-score of 3.091) in the platinum sensitive improved PFS group. QRT-PCR analysis of 31 HGSOC samples demonstrated a significant difference in PFS between low and high IRF1 expression groups (P=0.048) and between groups that were platinum sensitive versus not (P=0.016). In a larger validation data set, increased levels of IRF1 were associated with both increased PFS (P=0.043) and OS (P=0.019) and the effect on OS was independent of debulking status (optimal debulking, P=0.025; suboptimal, P=0.041).
    Conclusion: Transcriptome analysis identifies IRF1, a transcription factor that functions both in immune regulation and as a tumor suppressor, as being associated with platinum sensitivity and an independent predictor of both PFS and OS in HGSOC.
    Mesh-Begriff(e) Antineoplastic Agents/therapeutic use ; Cisplatin/therapeutic use ; Cystadenocarcinoma, Serous/drug therapy ; Cystadenocarcinoma, Serous/genetics ; Cystadenocarcinoma, Serous/mortality ; Disease-Free Survival ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Interferon Regulatory Factor-1/genetics ; Interferon Regulatory Factor-1/physiology ; Middle Aged ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/mortality ; Prognosis ; Survival Rate
    Chemische Substanzen Antineoplastic Agents ; IRF1 protein, human ; Interferon Regulatory Factor-1 ; Cisplatin (Q20Q21Q62J)
    Sprache Englisch
    Erscheinungsdatum 2014-09
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 801461-9
    ISSN 1095-6859 ; 0090-8258
    ISSN (online) 1095-6859
    ISSN 0090-8258
    DOI 10.1016/j.ygyno.2014.06.025
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Inhibition of the Nuclear Export Receptor XPO1 as a Therapeutic Target for Platinum-Resistant Ovarian Cancer.

    Chen, Ying / Camacho, Sandra Catalina / Silvers, Thomas R / Razak, Albiruni R A / Gabrail, Nashat Y / Gerecitano, John F / Kalir, Eva / Pereira, Elena / Evans, Brad R / Ramus, Susan J / Huang, Fei / Priedigkeit, Nolan / Rodriguez, Estefania / Donovan, Michael / Khan, Faisal / Kalir, Tamara / Sebra, Robert / Uzilov, Andrew / Chen, Rong /
    Sinha, Rileen / Halpert, Richard / Billaud, Jean-Noel / Shacham, Sharon / McCauley, Dilara / Landesman, Yosef / Rashal, Tami / Kauffman, Michael / Mirza, Mansoor R / Mau-Sørensen, Morten / Dottino, Peter / Martignetti, John A

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2016  Band 23, Heft 6, Seite(n) 1552–1563

    Abstract: Purpose: ...

    Abstract Purpose:
    Mesh-Begriff(e) Acrylates/administration & dosage ; Active Transport, Cell Nucleus/genetics ; Animals ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Resistance, Neoplasm/genetics ; Female ; Humans ; Hydrazines/administration & dosage ; Karyopherins/antagonists & inhibitors ; Karyopherins/genetics ; Mice ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Platinum/administration & dosage ; Platinum/adverse effects ; Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors ; Receptors, Cytoplasmic and Nuclear/genetics ; Triazoles/administration & dosage ; Xenograft Model Antitumor Assays ; Exportin 1 Protein
    Chemische Substanzen Acrylates ; Hydrazines ; KPT-185 ; Karyopherins ; Receptors, Cytoplasmic and Nuclear ; Triazoles ; selinexor (31TZ62FO8F) ; Platinum (49DFR088MY)
    Sprache Englisch
    Erscheinungsdatum 2016-09-20
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-16-1333
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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