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Posts Tagged ‘therapeutic proteomics’

Real Time Coverage Morning Session on Precision Oncology: Advancing Precision Medicine Annual Conference, Philadelphia PA November 2 2024

Posted in Artificial Intelligence Applications in Health Care, Artificial Intelligence in CANCER, Artificial Intelligence in Medicine - Applications in Therapeutics, Big Data, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Genomics, Clinical Genomics, Genomic Expression, Genomic Testing: Methodology for Diagnosis, Personalized and Precision Medicine & Genomic Research, Proteomics, REAL TIME Conference Coverage Twitter's Hashtags and Handles per Presentation/session, tagged , , , , , , , on November 4, 2024| Leave a Comment »

Real Time Coverage Morning Session on Precision Oncology: Advancing Precision Medicine Annual Conference, Philadelphia PA November 2 2024

Reporter: Stephen J. Williams, Ph.D.

9:20-9:50

How Can We Close the Clinical Practice Gaps in Precision Medicine?

Susanne Munksted, Diaceutics

Studies are showing that genetic tests are being ordered at a sufficient rate however it appears there are problems in interpretation and developing treatment plans based on omics testing results

 

  • 30 % of patients in past and now currently half of all patients are not being given the proper treatment based on genomic testing results (ASCO)
  • E.g. only 1.5% with NTRK fusions received a NTRK based therapy (this was > 4000 patients receiving wrong therapy)
  • A lung oncologist may only see one patient with NTRK fusion in three years

 

Precision Medicine Practice Gaps

48% of oncologist surveyed  agreed pathologist needs to be more informed and relevant in the decision making process with regard to tests needing to be ordered

95% said need to flip cost issues ; what does it cost not to get a test … i.e. what is the cost of the wrong therapy

We need a new commercialization model for therapeutic development for this new era of “n of one” patient

9:50-10:15

Implementation of a CLIA-based Reverse Phase Protein Array Assay for Precision Oncology Applications: Proteomics and Phosphoproteomics at the Bedside (CME Eligible)

Emanuel Petricoin, George Mason University

There are some tumor markers approved by FDA that cant just be measured by NGS and are correlated with a pathologic complete response

 

  • Many point mutations will have no actionable drug
  • Many alterations are post-genomic meaning there is a post translational component to many prognostic biomarkers
  • Prevalence of point mutation with no actionable mutation is a limit of NGS
  • It is important to look at phospho protein spectrum as a potential biomarker

 

Reverse phase protein proteomic analysis

  • Made into CLIA based array
  • They trained centers around the US on the technology and analysis
  • Basing proteomics or protein markers by traditional IHC requires much antibody validation so if the mass spectrometry field can catch up it would be very powerful
  • With multiple MRM.MS there is too low abundance of phosphoproteins to allow for good detection

 

They  conducted the I-SPY2 trial for breast cancer and determining if phosphoproteins could be a good biomarker panel

  • They found they could predict a HER2 response better than NGS
  • There were patients who were predicted HER2 negative that actually had an activated HER2 signaling pathway by proteomics so NGS must have had a series of false negatives
  • HER2 co phosphorylation predicts pathologic complete response and predicts therapy by herceptin
  • They found patients classified as HER2 negative by FISH were HER2 positive by proteomics and had HER2 activation

10:15-11:10

Liquid Biopsy MRD to Escalate or De-escalate Therapy (CME Eligible)

Adrian Lee

Adrian Lee, UPMC

Marija Balic, UPMC

Howard McLeod

Howard McLeod, Utah Tech University

Muhammed, Murtaza, University of Wisconsin-Madison

 

11:15-11:25  PRODUCT PRESENTATION  204A

SpaceIQ™ – Powering Next Generation Precision Therapeutics with AI-Driven Spatial Biomarkers

Dusty Majumdar, PredxBio 

Single Cell and Spatial Omics

 

  • Single cell transcriptomics technology have been scaled up very nicely over the past ten years
  • Spatial informatics field is lacking in innovations
  • Can get a terabyte worth of data from analysis of one slide

11:25-11:35  PRODUCT PRESENTATION  204C

10x Genomics

11:40-12:35

Transcriptomics and AI in Transforming Precision Diagnosis

Maher Albitar, Genomic Testing Cooperative

Transciptomica and AI:Transforming Precision diagnosis

-The Genomics Testing Coopererative at www.genomictestingcooperative.com

 

Advantages of transcriptomics

– mutation frequency and allele variant detection now at 80% (higher sensitivity in mutation detection)

 

– transcriptomics has good detection of chromosomal translocations

– great surrogate for IHC and detect splicing alterations

– can use AI to predict % of PDL1 in tumor cells versus immune cells

– they have developed a software UMAP (uniform manifold approximation and projection) to supervise cluster analysis

– the group has used AI to predict prognosis and survival using transcriptomics data

Marija Balic, UPMC

Andrew Pecora, Hackensack University Medical Center 

12:35-1:00

The Impact of Multi-Omics in the Context of the APOLLO-2 Moonshot Program (CME Eligible)

 

 

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Dark Cellular Receptors

Posted in Biological Networks, Gene Regulation and Evolution, Gene Regulation, Proteins, Proteomics, tagged , , , on November 13, 2015| Leave a Comment »

Dark Cellular Receptors

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Nov 10, 2015   GEN News Highlights

Unraveling the Mysteries of “Dark” Cellular Receptors   

http://www.genengnews.com/gen-news-highlights/unraveling-the-mysteries-of-dark-cellular-receptors/81251956/

 

  • A research team from the University of North Carolina School of Medicine (UNC) and University of California, San Francisco (UCSF) says it has created a general tool to probe the activity of orphan receptors, which are highly expressed in particular tissues but whose functions remain unknown. The team intends to illuminate the roles of orphan receptors in behavior and make them accessible for drug discovery.

    The creation of the research tool, which involves computer modeling, yeast- and mammalian cell-based molecular screening techniques, and mouse models, is published in an article (“Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65”) in Nature.

    According to Brian Shoichet, Ph.D., professor of pharmaceutical chemistry at UCSF, this work will help researchers learn how orphan receptors interact with molecules inside the body or with drugs. Specifically, the UNC and UCSF scientists used their new tool to find a novel probe molecule that can modulate the orphan G protein-coupled receptor 68 (GPR68, also known as OGR1), an orphan receptor that is highly expressed in the brain.

    “GPCRs are the single most important family of therapeutic drug targets,” said Dr. Shoichet. “About 27 percent of FDA-approved drugs act through GPCRs. They are considered to be among the most useful targets for discovering new medications.”

    The new probe molecule, dubbed “ogerin,” turns on GPR68, activating its signaling role. To understand how this activation of GPR68 affects brain function, the investigators gave it to mice and put them through a battery of behavioral tests. Mice that had been given ogerin were much less likely to learn to fear a specific stimulus. This fear-conditioning is controlled by the hippocampus, where GPR68 is highly expressed. But ogerin had no effect on mice that lacked this receptor.

    To demonstrate general research applicability, the UNC and UCSF researchers also used their technique to find molecules that can modulate GPR65, another orphan receptor.

    “We provide an integrated approach that we believe can be applied to many other receptors,” explained Bryan L. Roth, M.D., Ph.D., co-senior author of the Nature paper and the Michael Hooker Distinguished Professor of Protein Therapeutics and Translational Proteomics in the department of pharmacology at UNC. “The goal is to quickly find drug-like compounds for these receptors. This should facilitate discovery of novel and safer therapeutics for a host of diseases.”

    “We used yeast-based screening techniques to find compounds that activate an orphan receptor,” noted Xi-Ping Huang, Ph.D., co-first author and research assistant professor at UNC. “Then [co-first author] Joel Karpiak, a graduate student in Shoichet’s lab at UCSF, created a computer model and searched libraries of millions of compounds to find out what kind of molecular structure ensures proper binding and interaction with a specific receptor. Then, back in the lab, we tested new molecules and found a novel ligand.”

    “The fact that GPR68 is highly expressed in several tissues, especially the brain, and that it is a member of the large GPCR family, suggests that this discovery can be further leveraged for drug discovery,” added Dr. Shoichet.

    Currently, few drug developers would seek drugs for a target with an unknown role in human biology. With new evidence of the role of GPR68, and a molecule that can modulate that role, the door has been opened for further research studies, both basic and applied.

    “The druggable genome is an iceberg that is mostly submerged,” pointed out Dr. Shoichet. “This paper illuminates a small piece of it, providing new reagents to modulate a previously dark, unreachable drug target. Just as important, the strategy should be useful to many other dark targets in the genome.”

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