Publications

High-plex Proteomic Characterization of Pre-clinical models with the NULSAseq Mouse Panel 120

Product:

mouse, Neurology

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Topic/Product:

mouse, Neurology

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Abstract

Objectives: With the emergence of several preclinical models of neurodegenerative diseases including Alzheimer’s Disease (AD), proteomic characterization of these models is needed to better understand their clinical relevance and utility in therapeutic evaluation. Along with amyloid plaques and neurofibrillary tangles, neuroinflammation is an underlying mechanism of disease progression and a multiplex proteomics approach is needed to track the temporal regulation of inflammatory and neurodegenerative processes as well as the degree to which these preclinical models recapitulate the biology of the human disease.

Methods: Previously, we developed a 250-plex Inflammation Panel and 120-plex CNS Disease Panel on the automated ARGO platform to profile key proteins such as IL6, phospho-Tau, and amyloid beta for profiling of biofluids in human studies. To provide a complementary approach for proteomic profiling in preclinical models, we have developed a 120-plex Mouse Panel for detection of cytokines, growth factors and other CNS disease targets. Plasma samples from different mouse strains were assayed at multiple input volumes. CSF and brain lysates were also evaluated. Dilutional linearity, reproducibility and overall detectability were assessed. Additionally, various preclinical models of AD and Traumatic Brain Injury were also evaluated.

Results: Our results demonstrate robust performance with 5% median intra-assay CV and 97.4% detectability in mouse plasma samples from 5 common strains. Additionally, lowering sample input volume from 10uL to 5uL has minimal impact on overall detectability (>95%), reflecting high assay sensitivity. Dilutional linearity further demonstrated good target linearity with signal-to-noise ratio over 2 for 97% of the targets in the panel. The analytical validation along with the application of the panel across different AD models demonstrates the utility of the multiplex NULISAseq™ Mouse Panel for comprehensive characterization of neurodegenerative and inflammatory markers in preclinical models.

Authors & Affiliations

Xiao-Jun Ma1, Jianjia Fan2, Li Wang1, Hayeun Ji1, Wai Hang Cheng2, Tetiana Poliakova2, Carlos Barron2, Andrew Agbay2, Shweta Iyengar1, Sean Kim1, Niyati Jhaveri1, Xiaolei Qiu1, Bingqing Zhang1, Cheryl Wellington2, Yuling Luo1

1Alamar Biosciences Inc., Fremont, California, USA; 2University of British Columbia, Vancouver, BC Canada

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition. He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.