Ribosome Newsletter: Navigating the Convergence of Proteomics, AI, Synthetic Biology, and Translational Medicine
Welcome to this week's edition of Ribosome. In this issue we will explore studies on lung adenocarcinoma, revealing insights into its proteogenomic evolution, and examine new biomarkers for managing complications from cancer treatments. This issue also covers the role of deep learning in enhancing peptide sequencing and the impact of AI on protein design. Additionally, we provide updates on key industry events, including the Standard BioTools-SomaLogic merger, and analyze trends in the expanding markets of sample preparation and protein engineering. Stay informed with Ribosome for a comprehensive view of the proteomics field.
Biomarker Discovery
*Oncology
The study conducted a proteogenomic analysis of 197 lung adenocarcinoma cases, identifying the crucial role of chromosome 4q12 deletion in the transition from pre-invasive to invasive stages. This deletion downregulates SPATA18, impairing mitophagy and promoting tumor invasion. It also categorizes three proteomic subtypes and four immune clusters, delineating the molecular evolution in lung adenocarcinoma progression.
*Oncology
This study assessed the use of S100B and neurofilament light chain (NfL) in blood as indicators for CNS inflammation caused by immune checkpoint inhibitors (ICIs) in cancer patients. Involving 197 patients treated with CTLA-4 and PD-1 inhibitors for metastatic melanoma or renal cell carcinoma, it identified CNS inflammatory reactions (CNS irAE) in 4.6% of cases. Elevated S100B and NfL levels were observed during CNS irAE episodes, decreasing post-immunosuppression. S100B detected CNS irAE with 100% sensitivity, while NfL had a 79% sensitivity. Concurrent increases in C-reactive protein and liver enzymes (ALT/AST) were also noted. These findings suggest that S100B and NfL in blood can be effective biomarkers for early detection of ICI-induced CNS irAE
*Oncology
This proteogenomic study on 112 small cell lung cancer (SCLC) patients identified crucial genetic changes like FAT1 mutation, RB1 deletion, and 5q loss. It highlighted HMGB3's role in promoting cell migration and the link between ZFHX3 mutation and enhanced immune response. The analysis revealed four SCLC subtypes, each with specific therapeutic vulnerabilities, confirmed by drug tests on cell lines and xenografts, offering new avenues for targeted SCLC treatments.
*Metabolic Disorders
This study identified 37 key transcriptional regulators of lipid mobilization in human adipocytes, categorized into transcription factors, histone chaperones, and mRNA processing proteins. Focusing on ZNF189, a zinc finger protein, the research revealed its interaction with TRIM28 and its role in repressing the transcription of an adipocyte-specific isoform of phosphodiesterase 1B (PDE1B2). This repression was shown to be crucial for hormone-stimulated lipolysis in adipocytes. The findings highlight the ZNF189-PDE1B2 axis as a critical determinant in human adipocyte lipolysis and establish a link between chromatin architecture and lipid mobilization.
Proteomic Innovations
*Protein Design
This study introduces a method for designing complex all-α helical protein structures. Utilizing a combination of 18 helix-loop-helix motifs and canonical α-helices, the team generated a variety of α-helical structures, achieving five distinct topologies. These designed proteins demonstrated monomeric stability and accurately folded into their target structures. This innovative approach marks a significant advancement in protein design, enabling the creation of complex proteins with potential for diverse functional applications.
*Spatial Proteomics
The study introduces MAPS (Machine learning for Analysis of Proteomics in Spatial biology), a machine learning tool designed for efficient cell type annotation in spatial proteomics data. MAPS uses a neural network model to classify cells based on protein markers and cell size. Tested on MIBI and CODEX datasets for diseases like classic Hodgkin Lymphoma and diffuse large B cell lymphoma, MAPS outperformed existing methods in speed and accuracy. It effectively identified challenging cell types, including immune-origin tumor cells, with pathologist-level precision. The tool’s data efficiency and minimal computational resource demands make it valuable for tissue biology and disease research, demonstrating its applicability across various disease models and spatial proteomics platforms.
领英推荐
*Chemoproteomics
This study introduces a chemoproteomic technique using photoaffinity probes to precisely identify small-molecule binding sites on proteins within cells. By analyzing unique features of probe-modified peptides, researchers developed models for accurate site identification. This method creates an extensive map of binding sites on proteins, and integrates structural data to explore a variety of accessible sites for small molecules in native cellular environments. This advancement offers significant insights into small-molecule interactions at the molecular level.
*Peptide Sequencing
"Spectralis" is a new deep learning-based method designed to improve de novo peptide sequencing in mass spectrometry. It utilizes a convolutional neural network for predicting fragment ion series and estimating the Levenshtein distance of peptide sequences. This method has shown to enhance the sensitivity of peptide identification, nearly doubling the accuracy at 90% precision compared to existing techniques. Additionally, Spectralis has been effective in variant calling applications. Its development represents a notable step in advancing the capabilities of peptide sequencing and analysis within the field of proteomics.
Industry Update
*Merger
Standard BioTools Inc., known for its health technology solutions, has received shareholder approval for its impending merger with SomaLogic, as announced at a Special Meeting of Stockholders. The merger is expected to amplify Standard BioTools' market presence and strengthen its financial base, potentially delivering enhanced shareholder value. Michael Egholm, PhD, President and CEO of Standard BioTools, expressed optimism about the merger's positive impact on customer service and the company's growth trajectory.
*Market Research
The global sample preparation market is projected to hit $11.99 billion by 2030, advancing at a 6.4% CAGR. This growth is fueled by increasing demands in drug discovery and diagnostics, with notable advancements in technology enhancing laboratory automation. The market is dominated by the consumables segment, particularly in solid phase extraction techniques, and finds its largest application in drug discovery. North America, led by the U.S., remains the predominant region due to its focus on research and an aging population. The report underscores the pivotal role of pharmaceutical and biotech companies in driving market growth, influenced by the rising importance of genomics and proteomics research.
*Market Research
The protein engineering market is projected to surge from USD 3.18 billion in 2022 to USD 15.25 billion by 2032, growing at a robust CAGR of 16.97%. The market's expansion is driven by increasing demand in pharmaceuticals and healthcare for protein-based solutions, particularly in the development of novel therapeutics for chronic diseases like cancer. North America dominates this market, propelled by significant healthcare investments and a focus on innovative treatments. Key players are intensifying their R&D efforts and forming strategic partnerships, underpinning the market's rapid growth.
*Market Research
The Antibody Therapeutics market is forecasted to grow from $247.3 billion in 2023 to $479.0 billion by 2028, expanding at a CAGR of 14.1%. This growth is propelled by advances in antibody engineering and a surge in R&D, particularly in oncology antibody therapeutics. Europe, especially Germany, is expected to see significant growth. Key market players include F. Hoffmann-La Roche, AbbVie, and Johnson & Johnson, among others. The market is segmented by format, disease area, administration route, source, and end-user, with monoclonal antibodies and intravenous administration being predominant. This growth trajectory is supported by increasing collaborations and development initiatives in the sector.t
*Regulatory
AstraZeneca and Sanofi have received approval from China's National Medical Products Administration (NMPA) for their respiratory syncytial virus (RSV) immunization, Beyfortus, for infants. This makes Beyfortus the first RSV vaccine for infants in China, set to launch in late 2024. The vaccine, already approved in Europe and the U.S., is unique in its suitability for all infants, including those with health conditions or born preterm. Competitor Pfizer’s Abrysvo, another RSV prevention option for infants, is yet to be approved in China. AstraZeneca develops and manufactures Beyfortus, while Sanofi oversees commercialization. The approval was based on the efficacy demonstrated in three clinical trials, where Beyfortus showed consistent results in preventing RSV lower respiratory tract disease over a typical five-month RSV season.
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Co-Founder of Altrosyn and DIrector at CDTECH | Inventor | Manufacturer
10 个月The convergence of proteomics, AI, synthetic biology, and translational medicine is undeniably transformative for the biotech industry. As we witness the unveiling of molecular evolution in lung adenocarcinoma proteogenomics and the mapping of small-molecule binding sites through new chemoproteomic techniques, it's clear that we're at the forefront of groundbreaking discoveries. However, amidst this rapid progress, one can't help but ponder: How do we strike the right balance between innovation and ethical considerations in this ever-evolving landscape of biotechnology? How can we ensure that the potential benefits of these advances are equitably accessible to all, while addressing the complex ethical dilemmas that may arise?