作者: Tori, Kazuo ; Qu, Xuan ; Fallahi, Mohammad ; Wang, Ting ; Leong, Samantha ; Espinoza, Patricio ; Bell, Bryan ; Chen, Shuwen ; Covington, Mike ; Liu, Joseph ; Xing, Xiaoyun ; Li, Xuan ; Farmer, Andrew ; Du, Alan ; Mendoza, Raymond ; Xu, Peng ; Uchiyama, Tomoya ; Ryan, Yana ; Yun, Yue ; Anbunathan, Hima

AbstractSingle-cell omics has been widely applied in oncology research for biomarker discovery, providing an in-depth understanding of cancer heterogeneity. While bulk sequencing methods lack the specificity afforded by single cell studies, single cell applications miss insights due to trade-offs for sensitivity at scale. Current high throughput single cell DNA-seq applications are limited to targeted sequencing approaches, while scaled single cell RNA-seq applications are limited to 3’ or 5’ end counting methods or only capture polyadenylated RNA transcripts. To address these challenges, we have developed a nanoliter dispensing instrument, library prep chemistries and a bioinformatics analyses suite that scales both single cell genomics and transcriptomics assays while maintaining whole genome and whole transcriptome coverage, respectively. To demonstrate the ability to scale a non-targeted single cell whole genome amplification (WGA) application, we applied our new WGA workflow to cancer cell lines and primary Clear Cell Renal Cell Carcinoma samples. The data revealed segmental aneuploidies and both germline and putative somatic variants in thousands of single cancer cells in a single day, at shallow sequencing depths of approximately 300,000 paired end reads per single cell. Addressing the limitation of scaled single-cell transcriptomic solutions, our new total RNA-seq workflow is capable of generating data on up to 100,000 single cells at a time in two days. We applied this high-throughput workflow on cancer cells treated and untreated with epigenetic therapy and selected 11,000 cells to reach a deeper sequencing depth. The results demonstrate the ability to identify new biomarkers through comprehensive profiling of both protein-coding and noncoding genes with full gene-body coverage, revealing significant expression differences across multiple RNA biotypes as well as identifying splice junction isoforms. Overall, our data highlights the advantages of complex and rich datasets generated from single-cell workflows, which, when paired with an unbiased, non-targeted approach, enable the discovery of novel genomic and transcriptomic events in oncology samples.Citation Format:Shuwen Chen, Peng Xu, Xuan Li, Joseph Liu, Yana Ryan, Kazuo Tori, Hima Anbunathan, Alan Du, Mike Covington, Raymond Mendoza, Samantha Leong, Tomoya Uchiyama, Mohammad Fallahi, Xuan Qu, Xiaoyun Xing, Bryan Bell, Patricio Espinoza, Ting Wang, Yue Yun, Andrew Farmer. Resolving tumor heterogeneity by uncovering novel genomic and transcriptomic events with a new scaled and automated workflow [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB047.

2025-04-25·Cancer Research

Abstract LB316: Enabling long-read mRNA-seq for oncology biomarker discovery using limited clinical sample inputs

作者: Setthasap, Ploy ; Fallahi, Mohammad ; Peterson, Jackson ; Uchiyama, Tomoya ; Bell, Bryan ; Sevilla, Gilma ; Ryan, Yana ; Tori, Kazuo ; Du, Alan ; Yun, Yue ; Welter, Lisa ; Farmer, Andrew ; Covington, Mike ; Wei, Sherry ; Pasta, Saloni ; Yin, Shiyi

AbstractRNAs serve a central role in cellular biology by converting genomic information into effector molecules, either as mRNAs or directly functional RNAs. Measurement of RNA through RNA Sequencing has become an important method to understand biological processes. While it has been long appreciated that a vast diversity of RNA transcripts can be produced through alternative splicing, more recent work has defined a significant contribution of alternate and aberrant splicing to diseases like cancer, neurodegeneration, and autoimmunity. Thus, understanding the diversity of RNA transcripts is a key emerging topic in pathophysiology and biomarker discovery.Third-generation sequencing technologies provide the opportunity to sequence full-length cDNA without the need for fragmentation and hence provide a more complete picture of isoform structure and transcript abundance. However, a current limitation of long-read RNA sequencing (LR-RNA-seq) is the requirement for high input amounts of RNA that can be unachievable for some primary sample types, like RNA isolated from small amounts of tumor samples or sorted blood cancer cells.Here we describe a new LR-RNA-seq product enabling full-length RNA sequencing from single cells (∼10pg) up to 100 ng total RNA. With a 10ng total RNA input we demonstrate the ability to reliably sequence at an average length (N50) of 2kb and detection of full-length transcripts as long as 10kb. Performance at the single-cell level substantially outperforms existing single-cell LR-RNA-seq methods. Further, our data provides a more complete picture of isoform-specific changes compared to other commercially available technologies. With the ability to process up to 96 samples at a time, this technology will enable the processing of rare or valuable samples to uncover novel biomarkers beyond gene expression.Citation Format:Bryan Bell, Lisa Welter, Kazuo Tori, Jackson Peterson, Alan Du, Gilma Sevilla, Yana Ryan, Ploy Setthasap, Sherry Wei, Tomoya Uchiyama, Shiyi Yin, Mike Covington, Mohammad Fallahi, Saloni Pasta, Yue Yun, Andrew Farmer. Enabling long-read mRNA-seq for oncology biomarker discovery using limited clinical sample inputs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB316.

2025-04-21·Cancer Research

Abstract 6040: Exploring the impact of analytical factors on B-cell receptor profiling with high-throughput sequencing technologies

作者: Goyal, Shaveta ; BCR-SEQC consortium ; Izraelson, Mark ; Wan, Jun ; Song, Li ; Xiao, Wenming ; Zhang, Xiashiyao ; Pacheco, Miguel ; Ham, Henk-Jan van den ; Mallik, Rittika

AbstractThis abstract reflects the views of the authors and should not be construed to represent FDA’s views or policies.High-throughput sequencing of B-cell receptor (BCR) gene rearrangements, along with downstream analysis, provides researchers with the tools to define the B-cell clonal landscape and identify biomarkers for minimal residual disease (MRD). Despite significant advancements in the field over the past decade, comprehensive comparisons on different analytical methods, sequencing technologies, and bioinformatics tools remain largely unexplored.To bridge this gap, the FDA-led B-cell Receptor Sequencing Quality Control (BCR-SEQC) consortium developed protocols for generating reference materials derived from nine well-characterized B-cell lines and peripheral blood mononuclear cells (PBMCs) from healthy donors. This study aimed to evaluate the impact of key analytical factors—including input material quality and quantity, sequencing depth, sequencing technologies, and bioinformatics workflows—on BCR sequencing (BCR-seq) performance.The study employed multiple commercial BCR-seq products to prepare libraries with varying input amounts (25ng, 100ng, and 500ng) of reference materials. These libraries were sequenced using three different platforms: Illumina NextSeq 2000, ElementBio Aviti, and MGI DNBSEQ. Subsequently, four bioinformatics workflows (MiXCR, Immcantation, TRUST4, and IGX-Profile) were applied to assemble BCR sequences and determine clonotypes.This research provided the first comprehensive analysis of how variables in wet-lab and computational workflows influence sequencing-based BCR profiling, specifically in terms of linearity, accuracy, and sensitivity. Additionally, the study developed quality control (QC) metrics to ensure the robustness of assays and analytical workflows.Ultimately, this work highlights current capabilities and limitations in BCR-seq technology, identifies critical technical challenges, and establishes actionable best practices for reconstructing BCR repertoires from high-throughput sequencing data.Citation Format:Xiashiyao Zhang, Rittika Mallik, Miguel Pacheco, Shaveta Goyal, Mark Izraelson, Li Song, Henk-Jan van den Ham, Jun Wan, Wenming Xiao, BCR-SEQC consortium. Exploring the impact of analytical factors on B-cell receptor profiling with high-throughput sequencing technologies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6040.

项与 Takara Bio USA, Inc. 相关的新闻（医药）

2025-01-15

·Business Wire

Takara Bio USA Holdings, Inc. Announces the Acquisition of Curio Bioscience, Adding Spatial Biology to Its Broad Portfolio of Single-Cell Omics Solutions

SAN JOSE, Calif.--( BUSINESS WIRE )--Takara Bio USA Holdings, Inc. (“TBUSH”) today announced the acquisition of Curio Bioscience, a pioneering company in the field of spatial genomics. This strategic acquisition combines two innovative spatial biology platforms with Takara Bio’s industry-leading portfolio of single-cell genomics tools. TBUSH is a wholly owned subsidiary of Takara Bio Inc. ("Takara Bio"), a leading global biotechnology and life science company headquartered in Shiga, Japan. Takara Bio USA , Inc. ("TBUSA") is a wholly owned subsidiary of TBUSH. TBUSA and TBUSH are part of the global Takara Bio Group, which offers diverse life science products and services supporting discovery, translational, and clinical scientists in advancing their research. The Curio Bioscience acquisition will extend the power of Takara Bio’s NGS solutions and give customers deeper insights into tissue spatial organization and molecular composition. “We are proud of our history of innovation in the single-cell genomics market, having developed the first commercially available kits for single-cell RNA- and DNA-seq,” said Carol Lou, President and CEO of Takara Bio USA. “The acquisition of Curio Bioscience continues this legacy with the addition of Trekker, the first truly single-cell spatial technology.” Curio’s advanced Trekker and Seeker technologies integrate spatial information with molecular data, enabling researchers to transform single-cell sequencing data into spatially resolved maps. This transformation offers high-resolution insights into the organization and function of cells within their native tissue environments. “Curio Bioscience is dedicated to creating innovative approaches that map the entire transcriptome with unparalleled sensitivity and resolution,” said Stephen Fodor, co-founder and CEO. “Combining Curio’s technology with Takara Bio’s vast NGS and single-cell tool set will provide customers with industry-leading solutions for their spatial biology needs.” Through these advancements, Takara Bio has solidified its position as a leader in the single-cell genomics market by continually driving innovation and supporting groundbreaking research in the life science market for a wide range of applications in cancer biology, neuroscience, developmental biology, and immunology. Advisors Houlihan Lokey acted as exclusive financial advisor and Cooley LLP acted as legal advisor to Takara Bio. Aquilo Partners, L.P. acted as financial advisor and Dorsey & Whitney LLP as legal advisor to Curio Bioscience. About Takara Bio Takara Bio USA, Inc. is a wholly owned subsidiary of Takara Bio Inc. that manufactures and distributes kits, reagents, and instruments for the life sciences, including NGS, PCR, gene delivery, genome editing, stem cell research, nucleic acid and protein purification, and automated sample preparation. Takara Bio Inc., a world leader in biotechnology research and development, offers a host of life science research solutions, from enzymes and GMP-grade reagents to contracted cell and gene therapy manufacturing services and is the developer of the RetroNectin® reagent, a world standard in gene therapy protocols. Takara Bio is committed to preventing disease and improving the quality of life for all people through the use of biotechnology. For more information, visit takarabio.com . About Curio Bioscience Curio Bioscience is advancing a new generation of high-precision tools for the life sciences industry. The company has developed innovative spatial biology capabilities to map the whole transcriptome at high resolution using existing sequencing workflows and instrumentation. The founding team has a strong track record of bringing genomic solutions to market. Curio Bioscience is based in Palo Alto, California.

并购

2025-01-14

·SYNAPSE

Takara Bio USA Holdings, Inc. announces the acquisition of Curio Bioscience, adding spatial biology to its broad portfolio of single-cell omics solutions

Takara Bio USA Holdings, Inc. (“TBUSH”) today announced the acquisition of Curio Bioscience, a pioneering company in the field of spatial genomics. This strategic acquisition combines two innovative spatial biology platforms with Takara Bio’s industry-leading portfolio of single-cell genomics tools. TBUSH is a wholly owned subsidiary of Takara Bio Inc. ("Takara Bio"), a leading global biotechnology and life science company headquartered in Shiga, Japan. Takara Bio USA, Inc. ("TBUSA") is a wholly owned subsidiary of TBUSH. TBUSA and TBUSH are part of the global Takara Bio Group, which offers diverse life science products and services supporting discovery, translational, and clinical scientists in advancing their research. The Curio Bioscience acquisition will extend the power of Takara Bio’s NGS solutions and give customers deeper insights into tissue spatial organization and molecular composition. “We are proud of our history of innovation in the single-cell genomics market, having developed the first commercially available kits for single-cell RNA- and DNA-seq,” said Carol Lou, President and CEO of Takara Bio USA. “The acquisition of Curio Bioscience continues this legacy with the addition of Trekker, the first truly single-cell spatial technology.” Curio’s advanced Trekker and Seeker technologies integrate spatial information with molecular data, enabling researchers to transform single-cell sequencing data into spatially resolved maps. This transformation offers high-resolution insights into the organization and function of cells within their native tissue environments. “Curio Bioscience is dedicated to creating innovative approaches that map the entire transcriptome with unparalleled sensitivity and resolution,” said Stephen Fodor, co-founder and CEO. “Combining Curio’s technology with Takara Bio’s vast NGS and single-cell tool set will provide customers with industry-leading solutions for their spatial biology needs.” Through these advancements, Takara Bio has solidified its position as a leader in the single-cell genomics market by continually driving innovation and supporting groundbreaking research in the life science market for a wide range of applications in cancer biology, neuroscience, developmental biology, and immunology. Advisors Houlihan Lokey acted as exclusive financial advisor and Cooley LLP acted as legal advisor to Takara Bio. Aquilo Partners, L.P. acted as financial advisor and Dorsey & Whitney LLP as legal advisor to Curio Bioscience.

并购

2025-01-14

·SYNAPSE

Takara Bio USA Holdings, Inc. announces the acquisition of Curio Bioscience, adding spatial biology to its broad portfolio of single-cell omics solutions

并购

100 项与 Takara Bio USA, Inc. 相关的药物交易

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100 项与 Takara Bio USA, Inc. 相关的转化医学

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