SciLifeLab Clinical Genomics’ Post

A Major Milestone! I'm incredibly excited to share the publication of my first co-authored research paper: "Longitudinal multiomics analysis of aggressive pituitary neuroendocrine tumors: comparing primary and recurrent tumors from the same patient, reveals genomic stability and heterogeneous transcriptomic profiles with alterations in metabolic pathways" in Acta Neuropathologica Communications. In this study, we explored the complex biology of aggressive pituitary neuroendocrine tumors (PitNET) by comparing genomic, transcriptomic, and methylomic profiles between primary and recurrent tumors from the same patients. This work provides insights into the tumor's genomic stability over time and highlights potential therapeutic targets. I am truly grateful for the opportunity to contribute to this important research and extend my thanks to the team of co-authors who made this possible! 📄 You can read the full paper here: https://lnkd.in/gQ4bs9pB #FirstPublication #Research #PituitaryTumors #Science #Genomics #Transcriptomics #Neuroendocrinology #Milestone

The cost of #WholeGenomeSequencing is approaching that of the traditional genetic tests currently used for patients diagnosed with #AcuteLeukemia, according to a new study published in the Journal of Medical Economics. With costs falling and whole-genome sequencing adding new information that can improve treatment decisions, researchers see a future in which whole-genome sequencing becomes the standard for acute leukemias. – I think we will be there within the next year, especially since we have now introduced whole-genome sequencing routinely for children with leukemia. And we see in other ongoing studies we are performing that whole-genome sequencing finds everything clinically relevant that we need to identify with routine methods and adds important information. Information that allows us to say even more accurately which risk group the patient belongs to, which is important for prognosis and treatment. Whole-genome sequencing also provides data that we can explore to find new clinically relevant genetic abnormalities, says Valtteri Wirta, Head of Unit and Platform Scientific Director, Clinical Genomics Stockholm. The study was carried out by Genomic Medicine Sweden and the SciLifeLab Clinical Genomics platform. #PrecisionMedicine #microcosting https://lnkd.in/dXCQ-k64

https://lnkd.in/gpJnq-Xs   Article title: Response to first-line erlotinib in a false EGFR mutation-negative patient with non-small-cell lung cancer: Make no assumptions   Author(S): Caixia Deng, Hu Luo and Xiangdong Zhou*   Journal: Open Journal of Cell and Protein Science   Journal ISSN: 2994-4171 Abstract: So far, in the advanced non-small cell lung cancer (NSCLC) with clear epidermal growth factor receptor (EGFR) gene status, the treatment remmendations has reached an agreement: for patients with EGFR mutation-positive, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is the first choice, which can maximize the benefit from the treatment; while for the patients with wild-type EGFR gene, we should give priority to chemotherapy whether in the first-line or second-line therapy. However, about 70% of the patients were diagnosed at the late stage, so the pathological diagnosis and EGFR gene mutation detection depend on small specimens. Due to the limitations of small specimens, it may lead false EGFR mutation-negative, which results in these patients losing the opportunity to receive EGFR-TKI. Therefore, more simple and accessible predictors, in order to discover these potential false negatives of EGFR mutation, are urgently warranted. #Nonsmallcelllungcancer #EGFRTKI #FalseEGFRmutationnegative #Predictivemarker   #CellBiology #DevelopmentalBiology #Genetics #Immunology #Microbiology #MolecularBiology #Neuroscience #Oncology #ProteinScience #StructuralBiology #Peertechz #PeertechzPublications #TranslationalMedicine #GeneExpression #RNAMetabolism #NuclearOrganization #OrganelleBiogenesis #ProteinTrafficking #MembraneTrafficking #SignalTransduction #StemCellBiology #SystemsBiology #ComputationalCellBiology #CellAdhesion #CellMotility #CellularCommunication #CellCycle #CellDivision #CellGrowth #CellSurvival #CellDeath #CellStructure #CellDynamics #CellularDisease #Cytoskeleton #MolecularMotors

RNA-seq is a powerful technique that allows us to observe how the genome operates, orchestrating various events and activities at a higher level within the organism

🌟 Exciting News in the Fight Against FSHD! 🌟   We're thrilled to share our latest breakthrough in the treatment of Facioscapulohumeral Muscular Dystrophy type 2 (FSHD2) with you all! 🎉   Following our groundbreaking discovery of TIMP1 as the new driver gene in FSHD last year, our team at Bioada has been hard at work to push the boundaries of research in neuromuscular disorders. Today, we're proud to announce the publication of our latest paper unveiling a promising new avenue for FSHD2 treatment.   Our recent publication presents groundbreaking research aimed at unraveling the intricate pathology of FSHD2 and exploring novel therapeutic avenues. Through meticulous analysis of single-cell RNA sequencing data, obtained from primary myoblasts for FSHD2, we identified key dysregulated genes driving the progression of this condition.   Our findings revealed that Bisphenol S (BPS) and Bisphenol F (BPF) possess the remarkable ability to modulate the expression of crucial genes implicated in FSHD2. Specifically, BPS can upregulate 52 of the top downregulated genes, while BPF can upregulate 45 of these genes, with minimal impact on other gene expressions.   Furthermore, our enrichment analysis highlighted the profound involvement of these dysregulated genes in various facets of muscle biology, shedding light on potential therapeutic targets and pathways for intervention.   While our study represents a significant step forward in the quest for effective FSHD2 treatments, we recognize the need for further research to elucidate the precise mechanisms underlying the effects of BPS and BPF. Nonetheless, this discovery opens new doors for the development of targeted therapies that could alleviate the burden of FSHD2 on patients and their families.   At Bioada, we're committed to driving innovation and advancing the frontiers of science to combat rare diseases like FSHD. I extend my heartfelt gratitude to our dedicated team whose unwavering dedication made this achievement possible, and I'm eager to see how our findings pave the way for future breakthroughs in FSHD research.   Together, let's continue our journey towards a world where no disease goes undefeated. Stay tuned for more updates on our ongoing efforts to tackle FSHD and other challenging conditions. #FSHD #Research #Bioada #MuscularDystrophy #MedicalBreakthroughs 🧬💪 https://lnkd.in/eCbS4wKp

📍 Cellular atlas of the human ovary using morphologically guided spatial transcriptomics and single-cell sequencing Jones et al. systematically analyzed the spatial and cellular heterogeneity of the human ovary using samples from donors without a history of cancer, previous androgen therapy, or known diseases that affect ovarian function.   Key findings 🔹 Four major cell types and four immune cell subtypes 🔹 Distinct gene activities for oocytes, theca, and granulosa cells 🔹 Panels of oocyte-, theca-, and granulosa-specific genes expanding the knowledge of molecular programs driving follicle development 🔹 Previously unappreciated variation of hormone and extracellular matrix remodeling activities ➡ More details: https://lnkd.in/e3NW9KVX #UniversityofMichigan #spatialomics #spatialbiology #singlecellanalysis #singlecell

Integrative molecular and spatial analysis reveals evolutionary dynamics and tumor-immune interplay of in situ and invasive acral melanoma:- •In acral melanoma (AM), progression from in situ (AMis) to invasive AM (iAM) leads to significantly reduced survival. However, evolutionary dynamics during this process remain elusive. •Here, we report integrative molecular and spatial characterization of 147 AMs using genomics, bulk and single-cell transcriptomics, and spatial transcriptomics and proteomics. •Vertical invasion from AMis to iAM displays an early and monoclonal seeding pattern. The subsequent regional expansion of iAM exhibits two distinct patterns, clonal expansion and subclonal diversification. •Notably, molecular subtyping reveals an aggressive iAM subset featured with subclonal diversification, increased epithelial-mesenchymal transition (EMT), and spatial enrichment of APOE+/CD163+ macrophages. •In vitro and ex vivo experiments further demonstrate that APOE+CD163+ macrophages promote tumor EMT via IGF1-IGF1R interaction. Adnexal involvement can predict AMis with higher invasive potential whereas APOE and CD163 serve as prognostic biomarkers for iAM. Altogether, our results provide implications for the early detection and treatment of AM. #highlights :- •Invasion-preferred drivers and adnexal involvement predict early invasion of AMis. •Subclonal diversification accelerates the regional expansion of iAM. •APOE+/CD163+ macrophages promote tumor EMT via IGF1-IGF1R interaction. •APOE and CD163 staining is a prognostic biomarker for AM.

New blog by Maritta Räisänen on Studing the regulatory genome #myoma #uterineleiomyoma #tumorgenetics #cancerresearch. Check it out! You can subscribe to the Center of Excellence in Tumor Genetics blog and follow us on social media! https://lnkd.in/dkArd6vS

Mosaic structural variants (mSVs) in human aging A mystery surrounds how mosaic structural variants (mSVs) impact healthy tissues at the cellular level. This study sequenced over 1,000 single cells from 19 donors, revealing diverse mSVs in blood stem cells. Surprisingly, only those over 60 showed expanded mSV subclones. Cells with existing mSVs were more likely to acquire further variations. High-resolution cell typing identified eight distinct cell types. Expanded mSVs disrupted cellular function by misregulating pathways, favoring specific blood cell progenitors. This suggests mSVs contribute to aging-related changes in blood cell production and paves the way for understanding how they influence aging and disease risk in healthy tissues. The original article was published in Nat Genetics: https://lnkd.in/eXQhSvu2 https://lnkd.in/eKkpfi3V #genetics #genomics #precisionmedicine #genomicmedicine #dna #mosaicism #aging #longevity #blood #cancer #mutations #physiology #homeostasis #singlecell #hematopoieticstemcells #therapeutics #biomarkers #biotechnology #innovation #research #science #sciencecommunication

I am extremely proud to share our latest research from the Vascular Surgery unit at Karolinska Institutet, recently published in the European Heart Journal! This study combines genetic and molecular data from atherosclerotic plaques in the Biobank of Karolinska Endarterectomies (BiKE) to enhance risk stratification for patients with atherosclerosis. You can read the full study from the link below: Key Highlights: o  We identified three distinct risk groups each relating to a high, low and an intermediate risk profile. o  We discovered SNPs that act as eQTLs in mesenchymal cell phenotypes within the plaque, including several eQTLs associated with the ARNTL gene. o  Targeting the ARNTL gene in vascular smooth muscle cells in vitro resulted in decreased proliferation and a senescent-like phenotype. This study serves as a prototype for integrating clinical, genetic, and molecular features at single-cell resolution on a per-patient basis, allowing us to identify specific risk profiles and molecular targets within atherosclerotic plaques.I would like to extend my heartfelt thanks to Sofija Vuckovic, Clint Miller, Robert Wirka, Thomas Quertermous and all our co-authors and collaborators for their invaluable efforts and support! Interested in learning more? Check out the full study! #MedicalResearch #Cardiovascular #Genetics #PersonalizedMedicine