๐ฅ Last month, we launched the UK's first robotic genome testing facility for cancer patients with our partner Automata - a leading automation company powering automation in life sciences labs. This innovative installation will double our genetic testing capacity and expand the range of tests we perform within our existing lab space. ๐ฌ How does the technology work? Through Automataโs LINQ platform, sample pathways for saliva, tissue biopsies, blood and bone marrow are being automated. LINQ is a โsmartโ laboratory bench that houses and connects equipment using robotic and digital technology. Equipped with six robotic arms, the specialist cancer centreโs installation will substantially increase the throughput of the cancer testing lab without compromising on accuracy. It will primarily test for mutations in the BRCA genes, which can impact risk of various cancers including breast and ovarian. ๐ What impact will this have? With increased capacity thanks to automation, we will not only be able to process more somatic tests but also launch new genetic โ or cancer germline - testing. This type of genomic testing identifies inherited genetic changes that can increase risk of cancer and, for patients with the disease, can also be used to identify the right treatments. Patients at The Royal Marsden and beyond will benefit from increased access to genomic testing, which can help: - identify potential risk of cancer - diagnose the disease - and personalise treatments. By automating repetitive and time-consuming tasks, it will also give laboratory technologists and scientists more time for vital development work. Read more about this exciting new facility on our website: https://bit.ly/3x2B1G4
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๐๐ฑ๐๐ข๐ญ๐ข๐ง๐ ๐๐๐ฏ๐๐ง๐๐๐ฌ ๐ข๐ง ๐๐๐ง๐๐๐ซ ๐๐ซ๐๐ง๐ฌ๐๐ซ๐ข๐ฉ๐ญ๐จ๐ฆ๐ ๐๐ง๐๐ฅ๐ฒ๐ฌ๐ข๐ฌ Delving into the intricate landscape of cancer transcriptomes, a recent article from the Journal of Molecular Diagnostics unveils the power of Pacific Biosciences' Fusion and Long Isoform Pipeline (PB_FLIP) in unraveling isoform complexity. Kudos to Anthony R. Miller and team for their groundbreaking work! ๐ฒ๐๐ ๐ฐ๐๐๐๐๐๐๐: Genomic profiling with short-read sequencing has been instrumental, but the prevalence of structural variations in cancer demands enhanced resolution. Enter PB_FLIP, a sophisticated pipeline that leverages Pacific Biosciences' long-read RNA-sequencing (Iso-Seq) protocol. This protocol not only characterizes full-length isoforms but also identifies expressed fusion partners with remarkable precision. ๐จ๐ ๐๐๐๐๐๐๐๐ ๐๐ ๐ท๐ฉ_๐ญ๐ณ๐ฐ๐ท: PB_FLIP isn't just a pipeline; it's a game-changer. By incorporating a suite of RNA-sequencing software tools, it identifies fusion partners and resolves complex intragenic alterations. The study validates PB_FLIP's prowess by sequencing a commercial reference with known isoform complexity, showcasing high recall and benchmarking its performance. ๐พ๐๐ ๐ณ๐๐๐-๐น๐๐๐ ๐บ๐๐๐๐๐๐๐๐๐ ๐ด๐๐๐๐๐๐: The evolution from short to long-read sequencing is transformative. With PacBio's high-fidelity Iso-Seq protocols, the ability to routinely construct molecules up to 15,000 bp in size opens new avenues. The advantages include de novo assembly, full-length transcript characterization, and the resolution of structurally complex genomic regions. ๐ป๐๐๐๐๐๐๐๐๐๐๐๐ ๐ฐ๐๐๐๐๐: In the realm of pediatric and adolescent/young adult translational cancer research, Iso-Seq and PB_FLIP prove their mettle. From discovering novel expressed fusion partners to discriminating allele-specific expression profiles, the study underscores the utility of these technologies in complex structural variant deconvolution. ๐จ๐๐๐๐๐๐๐๐๐๐ ๐๐ ๐ฎ๐๐๐๐๐๐ ๐ท๐๐๐๐๐๐๐๐: The integration of Iso-Seq into the research protocol, along with PB_FLIP's customized pipeline, provides unparalleled resolution of expressed somatic structural variation, fusion transcripts, and diverse cancer-related isoforms. ๐ด๐๐๐๐๐ ๐๐๐๐๐ ๐ด๐๐๐๐๐๐: The precision of PB_FLIP is highlighted through comprehensive characterization of Iso-Seq data, emphasizing its application in pediatric/adolescent/young adult cases. Diagnostic fusion detection, isoform resolution, and identification of allele-specific expression become seamlessly achievable. ๐ด๐๐๐๐๐๐๐๐ ๐๐๐ ๐ด๐๐๐๐๐ ๐ ๐บ๐๐๐๐๐๐๐: Detailed methodologies, such as PacBio Iso-Seq sample preparation and Sequel sequencing, offer a glimpse into the meticulous approach undertaken in this groundbreaking research. #Genomics #Transcriptomics #PrecisionMedicine #CancerResearch #Bioinformatics #LongReadSequencing #PB_FLIP #IsoSeq
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Anti-aging research takes major leap forward thanks to unprecedented telomere tech High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer. Researchers from the Salk Institute have developed a groundbreaking technique called Telo-seq that is set to revolutionize our understanding of telomeres, the protective caps at the ends of our chromosomes. Telomeres play a crucial role in maintaining the integrity of our genetic material, but their repetitive nature and length have long posed challenges for scientists seeking to study them in detail. Telo-seq overcomes these hurdles by combining a clever molecular biology approach with state-of-the-art long-read sequencing technology. Telo-seq, in essence, is a method that allows researchers to sequence and analyze entire telomeres, along with a portion of the adjacent subtelomeric DNA, at an unprecedented level of resolution. The researcher used Telo-seq to resolve bulk, chromosome arm-specific and allele-specific human telomere lengths using Oxford Nanopore Technologiesโ native long-read sequencing. Telo-seq resolves telomere shortening in five population doubling increments and reveals intrasample, chromosome arm-specific, allele-specific telomere length heterogeneity. Telo-seq can reliably discriminate between telomerase- and ALT-positive cancer cell lines. Telo-seq is a tool to study telomere biology during development, aging, and cancer at unprecedented resolution. This innovative approach enables scientists to probe the composition and length of telomeres in a way that was previously impossible. By providing a high-resolution view of these crucial structures, Telo-seq promises to shed new light on the complex dynamics of telomeres during human development, aging, and disease. Scientists demonstrated the capabilities of Telo-seq across a range of cell types, including cancer cells, aging cells, and even induced pluripotent stem cells. Their findings reveal striking variations in telomere length not only between different cell types but also among individual chromosome arms and even between the maternal and paternal alleles of the same chromosome. https://lnkd.in/eMKJyspx
High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer - Nature Communications
nature.com
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Scientists Genetically Engineer Bacteria To Detect Cancer Cells: An international team of scientists has developed a new technology that can help detect (or even treat) cancer in hard-to-reach places, such as the colon. The team has published a paper in Science for the technique dubbed CATCH, or cellular assay for targeted, CRISPR-discriminated horizontal gene transfer. Engadget reports: For their lab experiments, the scientists used a species of bacterium called Acinetobacter baylyi. This bacterium has the ability to naturally take up free-floating DNA from its surroundings and then integrate it into its own genome, allowing it to produce new protein for growth. What the scientists did was engineer A. baylyi bacteria so that they'd contain long sequences of DNA mirroring the DNA found in human cancer cells. These sequences serve as some sort of one-half of a zipper that locks on to captured cancer DNA. For their tests, the scientists focus on the mutated KRAS gene that's commonly found in colorectal tumors. If an A. baylyi bacterium finds a mutated DNA and integrates it into its genome, a linked antibiotic resistance gene also gets activated. That's what the team used to confirm the presence of cancer cells: After all, only bacteria with active antibiotic resistance could grow on culture plates filled with antibiotics. While the scientists were successfully able to detect tumor DNA in mice injected with colorectal cancer cells in the lab, the technology is still not ready to be used for actual diagnosis. The team said it's still working on the next steps, including improving the technique's efficiency and evaluating how it performs compared to other diagnostic tests. In the future, the technology could also be used for targeted biological therapy that can deploy treatment to specific parts of the body based on the presence of certain DNA sequences. Read more of this story at Slashdot.
Scientists Genetically Engineer Bacteria To Detect Cancer Cells
science.slashdot.org
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Scientists Genetically Engineer Bacteria To Detect Cancer Cells: An international team of scientists has developed a new technology that can help detect (or even treat) cancer in hard-to-reach places, such as the colon. The team has published a paper in Science for the technique dubbed CATCH, or cellular assay for targeted, CRISPR-discriminated horizontal gene transfer. Engadget reports: For their lab experiments, the scientists used a species of bacterium called Acinetobacter baylyi. This bacterium has the ability to naturally take up free-floating DNA from its surroundings and then integrate it into its own genome, allowing it to produce new protein for growth. What the scientists did was engineer A. baylyi bacteria so that they'd contain long sequences of DNA mirroring the DNA found in human cancer cells. These sequences serve as some sort of one-half of a zipper that locks on to captured cancer DNA. For their tests, the scientists focus on the mutated KRAS gene that's commonly found in colorectal tumors. If an A. baylyi bacterium finds a mutated DNA and integrates it into its genome, a linked antibiotic resistance gene also gets activated. That's what the team used to confirm the presence of cancer cells: After all, only bacteria with active antibiotic resistance could grow on culture plates filled with antibiotics. While the scientists were successfully able to detect tumor DNA in mice injected with colorectal cancer cells in the lab, the technology is still not ready to be used for actual diagnosis. The team said it's still working on the next steps, including improving the technique's efficiency and evaluating how it performs compared to other diagnostic tests. In the future, the technology could also be used for targeted biological therapy that can deploy treatment to specific parts of the body based on the presence of certain DNA sequences. Read more of this story at Slashdot.
Scientists Genetically Engineer Bacteria To Detect Cancer Cells
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Uncovering Genetic Clues to Breast Cancer Chemo Response: Study Finds Mutations and Gene Expression Changes Linked to Neoadjuvant Treatment Efficacy This weekโs Implen NanoPhotometer Journal Club is highlighting the work published in 2024 by Yin et. al. using Illuminaโs NovaSeq technology to uncover molecular signatures of breast cancer tumors associated with chemotherapy response.ย Key findings of this study indicate neoadjuvant chemotherapy significantly alters mutation rates, DNA repair pathways, and immune microenvironment. Specifically, the CDKAL1P409L mutation was identified as reducing chemotherapy sensitivity, while amplifications in ADGRA2 or ADRB3 were linked with worse prognosis and treatment outcomes. This comprehensive analysis of genomic and transcriptomic changes in breast cancer tumors following neoadjuvant chemotherapy treatment reveals insights into the impact of chemotherapy on the molecular landscape of breast cancer. The findings highlight potential genetic biomarkers that provide understanding into chemotherapy resistance mechanisms and hold promise for guiding more personalized and effective treatments based on a patient's genetic profile. This study provided insights into breast cancer tumor adaptation and treatment response, paving way for genetics-guided improvements in prognostic predictions and treatment strategies. The NanoPhotometer was used in this study for the quantification of DNA and RNA. Specifically, after isolating total DNA from fresh frozen tissue samples and blood samples, and extracting RNA from fresh frozen tumor tissue, the purity of the total DNA and RNA was estimated using the NanoPhotometer. Visitย www.implen.deย to find out how the NanoPhotometer can improve your research. Authors: Gengshen Yin, Liyuan Liu, Ting Yu, Lixiang Yu, Man Feng, Chengjun Zhou, Xiaoying Wang, Guoxin Teng, Zhongbing Ma, Wenzhong Zhou, Chunmiao Ye, Jialin Zhang, Changhua Ji, Linfeng Zhao, Peng Zhou, Yaxun Guo, Xingchen Meng, Qinye Fu, Qiang Zhang, Liang Li, Fei Zhou, Chao Zheng, Yujuan Xiang, Mingming Guo, Zhigang Yu, Yongjiu Wang, Fei Wang and Shuya Huang. #NanoPhotometerย #JournalClub
Genomic and transcriptomic analysis of breast cancer identifies novel signatures associated with response to neoadjuvant chemotherapy - Genome Medicine
genomemedicine.biomedcentral.com
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What is making me optimistic today AI-Model Uses Gene Sequencing Data To Predict Primary Source of Cancer Researchers at Dana-Farber Cancer Institute have created an AI-based tool that uses tumor gene sequencing data to predict the primary source of a patientโs cancer. Theย study, published in inย Nature Medicine, suggests that this predictive tool, called OncoNPC, could help guide treatment of cancer and improve outcomes in difficult to diagnose cases. The primary source of cancer is traditionally diagnosed by a standardized diagnostic work-up, including radiology and pathology assessments based on slides of cells taken from a tumor biopsy. In 3-5% of cancer cases, the original source of the tumor cannot be determined. In these cases, patients are diagnosed with cancers of unknown primary (CUP) and have few treatment options because most treatments are approved for a specific type of cancer. โThis patient group has dismal outcomes,โ says Dana-Farber researcher and senior authorย Alexander Gusev, PhD. The team found that the AI modelโs predictions could have value for these patients. A retrospective analysis suggested that this additional piece of diagnostic information about the primary source of the tumor could help doctors select treatments that improve survival. โWe see the OncoNPC prediction as a nudge, a way to provide a possible explanation for the cancer that helps point to appropriate treatment, including precision medicine,โ says Gusev. OncoNPC, short for Oncology NGS-based Primary cancer type Classifier, accurately predicted the origin of about 80% of tumors with known types, including metastatic tumors, using a subset of cases that had not been used as training data. The model made high confidence predictions in 65% of the tumors, meaning it assessed its prediction as having a high probability of being correct. Those predictions were 95% accurate. They then applied OncoNPC to a separate database of 971 CUP tumors from patients seen at Dana-Farber, where a team of experts had already made a substantial effort to identify the primary source of the tumor. OncoNPC was able to predict the tumorโs origin with high confidence for 400 out of 971 (41.2%) of the cases. To validate these predictions, the team looked at inherited germline risks of cancer among these patients and found that the risks lined up with the predictions. Further, they looked at specific cases closely to determine if the data, including pathology results, patient history, and genetic mutations supported the prediction. https://lnkd.in/d2Hzq27m
Dana-Farber AI-model predicts primary source of cancer using gene sequencing data
dana-farber.org
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San Francisco's biotech scene sees a notable development as NOETIK, an AI-native biotechnology firm,ย integrates its human data atlas with a novel genomics platform, paving a new path in precision cancer immunotherapy. Central to this advancement is Perturb-Map, a spatial functional genomics technology. Developed by Dr. Maxime Dhainaut, in collaboration with the Icahn School of Medicine at Mount Sinai, Perturb-map facilitates the analysis of hundreds of genetically modified tumor clones in a single experiment. This technology is not just a scientific achievement but a tool that could potentially reshape our understanding of cancer biology. Noetikโs endeavor focuses on lung cancer, with an initial dataset of over 650 mutations. The application of Perturb-map in this context represents a significant leap in evaluating genetic variants' impacts in vivo, a critical step in developing targeted cancer therapies. Dr. Dhainaut sheds light on the challenges in functional genomicsโthe difficulty of conducting gene interrogation at scale within a relevant biological context. Noetikโs technology promises to bridge this gap, allowing in-depth analysis of gene function and interaction within the complex environment of human tissue. According to Dr. Jacob Rinaldi, CSO & Co-Founder of Noetik, there are limitations of current preclinical models in replicating human cancer biology. However, things are improving with a new paradigm of drug discovery where complex functional genetics and pharmacological hypotheses are tested in vivo, intertwined with advanced machine learning models. #WhereTechMeetsBio Image credit: NOETIK, Business Wire. In the image: Perturb-map deciphers the impact of genetic perturbations on the tumor phenotype. A. Selected images from a high-plex (25 ) immunofluorescence profiling of a mouse lung lobe carrying multiple cancer lesions. (Left Panel) Each tumor lesion carries a specific genetic perturbation, identified with Perturb-map. (Right Panel) This image highlights the immune composition of each tumor โ a subset of the phenotypic panel used to characterize tumor phenotypes. B. Magnification of the squared area from (A). The symbols (arrow, arrowhead and star) highlight corresponding tumors, visualized based on the perturbation (upper panel) or immune cell infiltration (lower panel).
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A comprehensive workflow for target adaptive sampling long-read sequencing applied to hereditary cancer patient genomes Innovations in sequencing technology have led to the discovery of novel mutations that cause inherited diseases. However, many patients with suspected genetic diseases remain undiagnosed. Long-read sequencing technologies are expected to significantly improve the diagnostic rate by overcoming the limitations of short-read sequencing. In addition, Oxford Nanopore Technologies (ONT) offers a computationally-driven target enrichment technology, adaptive sampling, which enables intensive analysis of targeted gene regions at low cost. In this study, we developed an efficient computational workflow for target adaptive sampling long-read sequencing (TAS-LRS) and evaluated it through application to 33 genomes collected from suspected hereditary cancer patients. Our workflow can identify single nucleotide variants with nearly the same accuracy as the short-read platform and elucidate complex forms of structural variations. We also newly identified SVAs affecting the APC gene in two patients with familial adenomatous polyposis, as well as their sites of origin. In addition, we demonstrated that off-target reads from adaptive sampling, which are typically discarded, can be effectively used to accurately genotype common SNPs across the entire genome, enabling the calculation of a polygenic risk score. Furthermore, we identified allele-specific MLH1 promoter hypermethylation in a Lynch syndrome patient. In summary, our workflow with TAS-LRS can simultaneously capture monogenic risk variants including complex structural variations, polygenic background as well as epigenetic alterations, and will be an efficient platform for genetic disease research and diagnosis. https://lnkd.in/gTQXVBhS
A comprehensive workflow for target adaptive sampling long-read sequencing applied to hereditary cancer patient genomes
medrxiv.org
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Scientists Genetically Engineer Bacteria To Detect Cancer Cells: An international team of scientists has developed a new technology that can help detect (or even treat) cancer in hard-to-reach places, such as the colon. The team has published a paper in Science for the technique dubbed CATCH, or cellular assay for targeted, CRISPR-discriminated horizontal gene transfer. Engadget reports: For their lab experiments, the scientists used a species of bacterium called Acinetobacter baylyi. This bacterium has the ability to naturally take up free-floating DNA from its surroundings and then integrate it into its own genome, allowing it to produce new protein for growth. What the scientists did was engineer A. baylyi bacteria so that they'd contain long sequences of DNA mirroring the DNA found in human cancer cells. These sequences serve as some sort of one-half of a zipper that locks on to captured cancer DNA. For their tests, the scientists focus on the mutated KRAS gene that's commonly found in colorectal tumors. If an A. baylyi bacterium finds a mutated DNA and integrates it into its genome, a linked antibiotic resistance gene also gets activated. That's what the team used to confirm the presence of cancer cells: After all, only bacteria with active antibiotic resistance could grow on culture plates filled with antibiotics. While the scientists were successfully able to detect tumor DNA in mice injected with colorectal cancer cells in the lab, the technology is still not ready to be used for actual diagnosis. The team said it's still working on the next steps, including improving the technique's efficiency and evaluating how it performs compared to other diagnostic tests. In the future, the technology could also be used for targeted biological therapy that can deploy treatment to specific parts of the body based on the presence of certain DNA sequences. Read more of this story at Slashdot.
Scientists Genetically Engineer Bacteria To Detect Cancer Cells
science.slashdot.org
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Sounds great