7 Works

A human IgSF cell-surface interactome reveals a complex network of protein-protein interactions

Woj Wojtowicz, Jost Vielmetter, Ricardo Fernandes, Dirk Siepe, Catharine Eastman, Gregory Chisholm, Sarah Cox, Heath Klock, Paul Anderson, Sarah Rue, Jessica Miller, Scott Glaser, Melisa Bragstad, Julie Vance, Annie Lam, Scott Lesley, Kai Zinn & Christopher Garcia
Cell-surface protein-protein interactions (PPIs) mediate cell-cell communication, recognition and responses. We executed an interactome screen of 564 human cell-surface and secreted proteins, most of which are immunoglobulin superfamily (IgSF) proteins, using a high-throughput, automated ELISA-based screening platform employing a pooled-protein strategy to test all 318,096 PPI combinations. Screen results, augmented by phylogenetic homology analysis, revealed ~380 previously unreported PPIs. We validated a subset using surface plasmon resonance and cell binding assays. Observed PPIs reveal a...

Evaluating the impact of early vs delayed ofatumumab initiation and estimating the long-term outcomes of ofatumumab vs teriflunomide in relapsing multiple sclerosis patients in Spain

Umakanth Vudumula, Mausam Patidar, Kapil Gudala, Elizabeth Karpf & Nicholas Adlard
To evaluate the impact of early (at first-line) vs delayed (3-year delay) ofatumumab initiation and long-term clinical, societal, and economic outcomes of ofatumumab vs teriflunomide in relapsing multiple sclerosis (RMS) patients from a Spanish societal perspective. A cost-consequence analysis was conducted using an Expanded Disability Status Scale (EDSS)-based Markov model. Inputs were sourced from ASCLEPIOS I and II trials and published literature. At the end of 10 years, compared with first-line teriflunomide treatment, early first-line...

Data from: High-resolution chemical dissection of a model eukaryote reveals targets, pathways and gene functions

Dominic Hoepfner, Stephen B. Helliwell, Heather Sadlish, Sven Schuierer, Ireos Filipuzzi, Sophie Brachat, Bhupinder Bhullar, Uwe Plikat, Yann Abraham, Marc Altorfer, Thomas Aust, Lukas Baeriswyl, Raffaele Cerino, Lena Chang, David Estoppey, Juerg Eichenberger, Mathias Frederiksen, Nicole Hartmann, Annika Hohendahl, Britta Knapp, Philipp Krastel, Nicolas Melin, Florian Nigsch, Edward J. Oakeley, Virginie Petitjean … & N. Rao Movva
Due to evolutionary conservation of biology, experimental knowledge captured from genetic studies in eukaryotic model organisms provides insight into human cellular pathways and ultimately physiology. Yeast chemogenomic profiling is a powerful approach for annotating cellular responses to small molecules. Using an optimized platform, we provide the relative sensitivities of the heterozygous and homozygous deletion collections for nearly 1800 biologically active compounds. The data quality enables unique insights into pathways that are sensitive and resistant to...

Data from: Identification and evaluation of novel acetolactate synthase inhibitors as antifungal agents

Daryl L. Richie, Katherine V. Thompson, Vivian Prindle, Thomas Aust, Ralph Riedl, Jianshi Tao, Jessica A. Sexton, Thomas Zabawa, Joseph Drumm, Simona Cotesta, Jürg Eichenberger, Sven Schuierer, Nicole Hartmann, N. Rao Movva, John A. Tallarico, Neil S. Ryder & Dominic Hoepfner
High-throughput phenotypic screening against yeast Saccharomyces cerevisiae revealed a series of triazolo-pyrimidine-sulfonamide compounds with broad-spectrum antifungal activity, no significant cytotoxicity, and low protein binding. To elucidate the target of this series we have applied a chemogenomic profiling approach using the S. cerevisiae deletion collection. All compounds of the series yielded highly similar profiles that suggested acetolactate synthase (Ilv2p, catalyzes the first common step in branched chain amino acid biosynthesis) as a possible target. High correlation...

Systematic dissection of transcriptional regulatory networks by genome-scale and single-cell CRISPR screens

Kathleen Sprouffske, Rui Lopes, Caibin Sheng, Esther C. H. Uijttewaal, Adriana Emma Wesdorp, Jan Dahinden, Simon Wengert, Juan Diaz-Miyar, Umut Yildiz, Melusine Bleu, Verena Apfel, Fanny Mermet-Meillon, Rok Krese, Mathias Eder, André Vidas Olsen, Philipp Hoppe, Judith Knehr, Walter Carbone, Rachel Cuttat, Annick Waldt, Marc Altorfer, Ulrike Naumann, Joachim Weischenfeldt, Antoine DeWeck, Audrey Kauffmann … & Giorgio G. Galli
Millions of putative transcriptional regulatory elements (TREs) have been cataloged in the human genome, yet their functional relevance in specific pathophysiological settings remains to be determined. This is critical to understand how oncogenic transcription factors (TFs) engage specific TREs to impose transcriptional programs underlying malignant phenotypes. Here, we combine cutting edge CRISPR screens and epigenomic profiling to functionally survey ≈15,000 TREs engaged by estrogen receptor (ER). We show that ER exerts its oncogenic role in...

Application of simultaneous selective pressures slows adaptation

Lauren Merlo, Kathleen Sprouffske, Taylor Howard, Kristin Gardiner, Aleah Caulin, Steven Blum, Perry Evans, Antonio Bedalov, Paul Sniegowski & Carlo Maley
Background and objectives: Beneficial mutations that arise in an evolving asexual population may compete or interact in ways that alter the overall rate of adaptation through mechanisms such as clonal or functional interference. The application of multiple selective pressures simultaneously may allow for a greater number of adaptive mutations, increasing the opportunities for competition between selectively advantageous alterations, and thereby reducing the rate of adaptation. Methodology: We evolved a strain of Saccharomyces cerevisiae that could...

Evaluating the impact of early vs delayed ofatumumab initiation and estimating the long-term outcomes of ofatumumab vs teriflunomide in relapsing multiple sclerosis patients in Spain

Umakanth Vudumula, Mausam Patidar, Kapil Gudala, Elizabeth Karpf & Nicholas Adlard
To evaluate the impact of early (at first-line) vs delayed (3-year delay) ofatumumab initiation and long-term clinical, societal, and economic outcomes of ofatumumab vs teriflunomide in relapsing multiple sclerosis (RMS) patients from a Spanish societal perspective. A cost-consequence analysis was conducted using an Expanded Disability Status Scale (EDSS)-based Markov model. Inputs were sourced from ASCLEPIOS I and II trials and published literature. At the end of 10 years, compared with first-line teriflunomide treatment, early first-line...

Registration Year

  • 2022
    2
  • 2021
    1
  • 2020
    2
  • 2013
    2

Resource Types

  • Dataset
    7

Affiliations

  • Novartis (Switzerland)
    7
  • Fred Hutchinson Cancer Research Center
    1
  • University of Pennsylvania
    1
  • Ontario Genomics Institute
    1
  • Stanford University
    1
  • Stanford University School of Medicine
    1
  • Genomics Institute of the Novartis Research Foundation
    1
  • Friedrich Miescher Institute
    1
  • Children's Hospital of Philadelphia
    1
  • Lankenau Institute for Medical Research
    1