The Arkansas Bioinformatics Consortium (AR-BIC)
The Arkansas Bioinformatics Consortium (AR-BIC), which is an alliance consisting of the five research universities in Arkansas, namely, UAMS, UALR, UAPB, ASU, UAF, as well as the FDA's National Center for Toxicological Research (NCTR), is excited and commits to supporting the Blood PAC. Our group pledges to share data from an on-going clinical trial composed of different cohorts and utilizing liquid biopsies, with the aim to better understand cell free DNA (cfDNA) in health and disease. The lung cancer cohort (enrollment in progress) will involve 30 de-identified patients, along with molecular profiling from: i) solid tumor and ii) blood/plasma. Solid tumor material will be subjected to extensive molecular profiling by: i) DNA sequencing via low-pass WGS and high-coverage custom NSCLC gene panel, ii) RNA-seq, and iii) methylation (EPIC) array analysis. Blood/plasma samples will be analyzed for circulating tumor DNA (ctDNA) by digital droplet PCR (ddPCR) and/or NGS methods. Lung cancer cohort blood collection will include a pre-operative or pre-systemic therapy specimen, and then multiple post-treatment specimens collected monthly. In addition, an extra Streck tube of blood will be collected with every draw, and overnight shipped to the Kuhn Lab at USC for High-Definition Single Cell Analysis (HD-SCA). To improve the scientific understanding of cfDNA, a single blood/plasma collection will be obtained from the following cohorts for NGS analysis: i) 30 heavy smokers (> 30 pack years) without cancer, ii) 30 patients with known inflammatory disease (Hepatitis C or Rheumatoid Arthritis), iii) 30 normal volunteers before and after ~30-45 minutes of cardio-level exercise. With these cohorts, an extra Streck tube of blood can be collected, and overnight shipped to USC for HD-SCA. We are committed to sharing scientific data and analyses from these cohorts with the Blood PAC.
In support of the Blood Profiling Atlas, AstraZeneca will provide standard operating procedures for ctDNA isolation and library construction for targeted and whole genome/exome sequencing of ctDNA. The AstraZeneca bioinformatics pipeline for variant calling in ctDNA is available for all interested parties. Furthermore, AstraZeneca will generate ctDNA for comparative studies of other bioinformatics pipelines with the goal to develop best practices in identifying variants in ctDNA after high depth sequencing that will standardize analyses of data acquisition for the Atlas. AstraZeneca will additionally provide data on method comparisons and can assist in data generation for samples provided to this project.
Biodesix is commited to share selected genomic and proteomic data, share published analytical and clinical validation data for their developed liquid biopsy strategies, share SOPs and strategies for blood collection, sample processing and sample analysis for their liquid biopsy tests, including EGFR, KRAS, BRAF, ALK, Ret and Ros. They plan to, wherever possible, share de-identified raw data derived from previously published proteomic testing. Biodesix also commits to offer in-kind support up to a value of $100,000 relating to experience and expertise in statistics, quality assurance, regulatory issues, clinical testing and business/business development.
Breast Cancer Research Foundation (BCRF)
On December 20, 2016 The Breast Cancer Research Foundation (BCRF) announced its commitment to advancing the understanding of metastatic disease in patients through their support of the Blood Profiling Atlas in Cancer (Blood PAC). “The Cancer Moonshot, which helped inspire the Blood PAC initiative, exemplifies a core principle upon which the BCRF was founded: progress toward a future without cancer through cooperation and collegiality as well as scientific excellence,” Dr. Larry Norton, BCRF Scientific Director and Medical Director of the Evelyn H. Lauder Breast Center at Memorial Sloan Kettering Cancer Center. BCRF has awarded a team science grant to Drs. Shriver and Kuhn from the Department of Defense’s Murtha Cancer Center and the University of Southern California.The funds have been awarded to recognized leaders in biomarker assay validation and are intended to support pilot projects that will utilize multiple technologies for analyzing rare events in the blood of cancer patients and subsequently deposit the data and associated protocols into the Blood PAC commons. BCRF believes that Blood PAC is uniquely qualified and in position to establish an open database for liquid biopsies in order to expedite the development of safe and effective blood profiling diagnostic technologies to accelerate drug development, streamline clinical research, and dramatically improve the lives of cancer patients.
The Center for Data-Driven Discovery in Biomedicine (D3b) on behalf of Children’s Hospital of Philadelphia (CHOP)
The Center for Data-Driven Discovery in Biomedicine (D3b) on behalf of Children’s Hospital of Philadelphia (CHOP) is committed to supporting the development of blood profiling biomarker research and its clinical implementations through the integration and inclusion of pediatric cancer patient populations in BloodPAC. In collaboration with partnered consortia, CHOP and member institutions of the Children’s Brain Tumor Tissue Consortium (CBTTC), Pacific Pediatric Neuro-Oncology Consortium (PNOC) will share and integrate data generated from blood/plasma circulating tumor DNA profiling efforts collected from pediatric brain tumor patients. D3b has several hundred serially collected samples in the context of clinical trial consortiums and a much larger set of processed blood and plasma samples at CHOP collected under research protocols that have yet to be fully leveraged. Data shared will include collection and processing protocols as well as the resulting genomic and analyzed data from 50 initial samples with the expectation of growing to approximately 500 samples over the next two years. Furthermore, CHOP commits to the shared implementation of best practices with BloodPAC members, including data harmonization and integration through its pediatric data commons initiatives. Alongside the blood profiling data and through integrative data commons, CHOP will also provide available whole genome sequencing (plasma, tumor and normal) and RNA-seq (tumor) for the same set of patients. Early efforts will focus on pediatric brain tumors and as standard protocols are developed through efforts like BloodPAC, CHOP will be expanding efforts across all pediatric cancers and additional rare diseases of interest.
College of American Pathologists (CAP)
The Pre-analytics for Precision Medicine Project Team of the College of American Pathologists (CAP) will provide expert input on pre-analytical factors related to cancer patient blood samples at the point of care and in the pathology laboratory to assure that they are fit for purpose and will work with partners to achieve the goals of optimization and implementation of standardized pre-analytical procedures for blood profiling platforms in CAP-accredited laboratories.
CytoLumina Technologies Corp. is on a mission to make dramatic improvements in cancer patient quality of life through its patented high sensitivity liquid biopsy nanotechnology for cancer detection and monitoring. In a partnership with UCLA Health Systems and Cedars-Sinai Medical Center (CSMC), CytoLumina has been developing its proprietary CytoTrapNano™ CTC Assays (also known as “NanoVelcro” CTC Assays) for highly sensitive enumeration and molecular characterization of CTCs in prostate cancer, hepatocellular carcinoma, and pancreatic cancer. To support the Blood Profiling Atlas, CytoLumina will release and share its sample preparation protocols, pre-analytical data for FDA IDE submission, unprocessed CTC microscopy images from 1000 CTC studies, and morphologic characterizations on thousands of CTCs. Through a long-standing collaboration with the Urologic Oncology Program of the Samuel Oschin Comprehensive Cancer Institute at CSMC, our collaborative team identified a subpopulation of CTCs morphologically identified by distinctly smaller nuclei that we have named very-small-nuclear CTCs (vsnCTCs). The presence of vsnCTCs is strongly associated with the visceral metastasis in prostate cancer- a clinical event tied to aggressive biology and extremely short survival. With the UCLA Surgery Program, the joint team has been exploring the use of CTC enumeration for diagnosis and staging of hepatocellular carcinoma and pancreatic cancer, and evaluating its promise to guide the selection of patients for curative liver transplantation and pancreatectomy, respectively.
Eli Lilly and Company
Eli Lilly and Company is studying approaches for the profiling of exosomes for mRNA and non-coding RNA expression. Lilly will share sample preparation methods, next-generation quantitative PCR-based methods, and Next Generation Sequencing-based methods, along with data related to disease characterization through gene expression analysis.
Epic Sciences is committed to supporting the Blood Profiling Atlas and will share data on circulating tumor cells in prostate cancer cohorts from the Memorial Sloan Kettering Cancer Center and the Prostate Cancer Clinical Trials Consortium. The data set will include information from thousands of CTCs across multiple lines of therapy. It has been increasingly acknowledged that the cellular diversity of cancer is a key feature of the disease that has blunted the effectiveness of many new classes of drugs. The CTC data to be contributed will shed new light on the diversity of circulating tumor cells in late stage prostate cancer. This data will also provide novel insights as to how numerous CTC species correlate with response or resistance to standard of care treatments. In addition, Epic Sciences will bring its unique expertise in blood processing and long term preservation of circulating tumor cells and leukocytes for complex biomarker analysis.
The strategy of developing an open, well-curated public database would be similar to the database that FDA reviewed in clearing a next-generation sequencing based cystic fibrosis (CF) test nearly three years ago. This Blood Profiling Atlas could have the appropriate controls that would allow it to be recognized by FDA as a source of valid scientific evidence, as proposed in FDA's draft guidance document "Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing (NGS)-Based In Vitro Diagnostics”.
Foundation Medicine continues to support the Cancer Moonshot to accelerate research in precision medicine with the goal of advancing patient care. In this most recent endeavor, Foundation Medicine will share with the Blood Profiling Atlas data generated from analytic validation studies of FoundationACT, including analysis using cell line models and real world patient samples. FoundationACT is Foundation Medicine’s best-in-class, hybrid capture, blood-based diagnostic for circulating tumor DNA. It is optimized to detect all four classes of clinically relevant genomic alterations (base substitutions, insertion/deletions, copy number alterations and gene fusions) with unparalleled accuracy of 99% sensitivity and 99% specificity (PPV). Foundation Medicine’s release of any and all data to the Blood Profiling Atlas is de-identified and HIPPA-compliant. Foundation Medicine has also committed its subject matter experts, including its bioinformatics team, to offer expertise needed as this project is implemented.
Genomic Health, Inc is a leading developer of diagnostic tests that provide proven benefit to patients through individualized cancer treatment, sharing the mission of precision medicine with the Cancer Moonshot. Genomic Health will support the Blood Profiling Atlas with data produced using Oncotype SEQ Liquid Select, a next-generation sequencing based test that detects actionable genetic variants in cell-free circulating DNA from patients with advanced cancer. Oncotype SEQ Liquid Select assesses single nucleotide variants, insertions/deletions, gene rearrangements and copy number variations in a targeted panel of cancer genes with high specificity at the sample level (> 99% for all 4 variant classes) and sensitivity (95% level of detection is < 1% mutant allele frequency for single nucleotide variants, indels and rearrangements, and < 3 copies for copy number variants). Shared data will come from analyses of nonclinical and preclinical validation samples, and from routine clinical testing performed in Genomic Health's commercial laboratory. Our technical, analytical and clinical experts look forward to working with the Blood Profiling Atlas teams. These contributions will continue as our clinical studies mature and clinical experience grows.
Guardant Health is committed to supporting the Blood Profiling Atlas by contributing pre-analytical and genomic data generated from 500 real-world clinical lung cancer patient samples tested by Guardant360, the world’s first comprehensive liquid biopsy. Guardant360 uses Digital Sequencing, an error suppressing hybrid-capture next-generation sequencing platform, to simultaneously achieve ultra-high sensitivity and specificity across single-nucleotide, copy-number, insertion/deletion, and structural variants. Guardant360 has been used by >90% of the leading cancer centers in the United States, as well as by thousands of oncologists for nearly 30,000 patients in routine clinical care. Guardant Health is also happy to collaboratively share expertise in reference standards, rare-analyte molecular biology, bioinformatics, and biostatistics.
Lexent Bio, Inc.
Lexent Bio is committed to supporting the Blood Profiling Atlas in Cancer and improving the lives of cancer patients. Lexent will share protocols and data from 30 patients who underwent intent-to-cure surgery for early stage cancers, including whole genome sequencing of tissue biopsies, pre and post surgery cfDNA, and buffy coat sequencing, as well as WGS data from over 50 samples to compare sequencing quality metrics of cfDNA extracted from fresh vs. frozen plasma. Additionally, Lexent is offering the expertise of its team of clinical, bioinformatics, laboratory, and technology experts to support the initiative.
Memorial Sloan Kettering Cancer Center
Encouraged by the Cancer Moonshot initiative, Memorial Sloan Kettering Cancer Center (MSK) will share our methods of blood sample collection and the comparative results of different processing methods for cell-free nucleic acid analysis. With the aim of developing the atlas, MSK will share data on circulating tumor cells (CTC) obtained from metastatic prostate cancer patients at decision points in management when a change in systemic therapy is needed. The approach will shed light on the influence of prior treatment on outcome. Further characterization of the cells both at the phenotypic level and genomic level will also provide insights into the sensitivity of an individual patient's disease to different types of therapy, enabling clinicians to better guide therapy and improve patient outcomes.
Novartis is evaluating the performance of different methods to test circulating tumor DNA ("ctDNA") including PCR-based methods and Next Generation Sequencing-based methods. Novartis will share (i) standard operating procedures for plasma collection for ctDNA; (ii) results from evaluation of different commercially available ctDNA extraction kits (iii) evaluation of ctDNA technology performance using contrived samples. In addition, Novartis will share data and/or samples generated from these evaluations.
Open Commons Consortium (OCC)
Open Commons Consortium (OCC) in collaboration with the University of Chicago commits to organizing and operating an open Blood Profiling Atlas Commons. The Commons will be based upon the same open source software stack used by the NCI Genomic Data Commons so that the genomic, image and clinical data in the Commons can be shared with the appropriate security, privacy and compliance controls. To facilitate the rapid development of this critical resource, the OCC / University of Chicago team will contribute up to six months of engineering, bioinformatics and project management resources to the project and up to $500,000 of compute and storage resources for building the commons and for the use of the commons by the research community.
Personal Genome Diagnostics
Personal Genome Diagnostics (PGDx) is committed to realizing the potential of liquid biopsy to improve the lives of cancer patients. PGDx will strongly support the Blood Profiling Atlas and will share expertise, protocols, and non-proprietary ctDNA profiling data generated with their PlasmaSELECT platform. PGDx will submit data from 500 samples during the pilot phase of the Blood Profiling Atlas and work with their academic, pharma/biotech, and molecular lab partners to enable their contribution of data to the Atlas. Additionally, PGDx is offering the expertise of its team of genomic, computational, and diagnostic scientists to support the initiative.
Pfizer intends to share de-identified data from cfDNA analysis (digital PCR) of clinical trial samples from two different clinical programs, subject to internal approvals for public disclosure. Data from one of the clinical programs, anticipated to be available in a six to nine month time frame, will be derived from a Phase 3 trial in breast cancer and will include clinical outcome and baseline characteristics, as well as data from cfDNA analysis, on 395 patients. Similar data from the second clinical program involving an ongoing Phase 1 / 2 NSCLC trial is anticipated to be available to share the latter half of 2017 to 2018, pending publication and regulatory approvals, for 40 and 200 patients for Phase 1 and Phase 2, respectively.
Prostate Cancer Foundation (PCF)
On December 20, 2016 the Prostate Cancer Foundation (PCF) announced its commitment to advancing the understanding of metastatic disease in patients through their support of the Blood Profiling Atlas in Cancer (Blood PAC). “PCF has been funding blood-based biodetection of cancer DNA activity since 2008. Our new partnership with BCRF will accelerate a more comprehensive understanding of real-time metastatic disease activity. Support for Blood PAC exemplifies PCF’s commitment to rapid data sharing and team science across all cancer types,” Jonathan W. Simons, MD president and CEO, PCF.
PCF is supporting Dr. Howard I. Scher of Memorial Sloan Kettering Cancer Center (MSKCC) and the Prostate Cancer Clinical Trials Consortium (PCCTC). The funds have been awarded to recognized leaders in biomarker assay validation and are intended to support pilot projects that will utilize multiple technologies for analyzing rare events in the blood of cancer patients and subsequently deposit the data and associated protocols into the Blood PAC commons. PCF believes Blood PAC is uniquely qualified and in position to establish an open database for liquid biopsies in order to expedite the development of safe and effective blood profiling diagnostic technologies to accelerate drug development, streamline clinical research, and dramatically improve the lives of cancer patients.
Seven Bridges will contribute its experience in accelerating pharmaceutical research and development and in building national-scale research systems by developing the Blood Profiling Atlas Analysis Cloud, specifically tailored to the needs of the liquid biopsy community. This environment – based on the company’s work partnering with the NCI, Genomics England, the VA and others – will integrate with the Blood Profiling Atlas Commons, allowing molecular, clinical and imaging data to be easily, securely, and cost effectively analyzed by researchers across disciplines. In addition, Seven Bridges will share its expertise in cancer genomics and immunoinformatics analysis. To do so, the company will release algorithms for analyzing liquid biopsy data at scale, committing six months of engineering, bioinformatics and project management resources, and up to $500,000 compute and storage resources to facilitate use of the analysis tools and data donated by the Blood Profiling Atlas community.
Streck has been a leader in the field of liquid biopsy for 13 years with the invention of the CellSave Preservative tube used in the isolation of CTCs in the CELLSEARCH® system in 2004 and the first cell-free DNA specific blood collection tube, Cell-Free DNA BCT®, in 2009. Additionally, Streck has active relationships with many BloodPAC consortium members, which provides valuable insight on the actual sample stabilization and transportation needs of key players in the field. Thus, Streck plays a unique role in the standardization of pre-analytical variables related to liquid biopsies with its specialized knowledge of cellular and nucleic acid stabilization in whole blood. Streck will apply this knowledge to assist the BloodPAC consortium in the standardization of pre-analytical variables in the oncology liquid biopsy space.
Sysmex Inostics is committed to accelerate the broad implementation of liquid biopsy testing capabilities by providing globally available IVD products and services. Sysmex Inostics would like to extensively support the Blood Profiling Atlas by sharing data and expertise, generated by the BEAMing and SafeSeqS technology. Firstly, Sysmex Inostics would like to submit data form a pre-analytics study including normal individuals as well as colon cancer patients. In this study, we have analyzed the effect of various pre-analytical parameters on the stability of circulating tumor DNA and propose specific collection & transportation conditions. Additional testing of these conditions for other cancer types are currently ongoing and the data would also been made available to BPA at a later time point. In addition to pre-analytical validation data, Sysmex Inostics is also continuously generating data that support the clinical validity and utility of circulating tumor DNA testing. These data sets could also complement the data generated by other technologies. In summary, Sysmex Inostics is offering its comprehensive expertise in analyzing circulating tumor DNA using highly sensitive technologies as well as taking these technologies from the clinical research field to the benefit of patients.
Thermo Fisher Scientific
Thermo Fisher Scientific is enthusiastic about the Blood Profiling Atlas and will contribute a combination of internal and customer validation data sets on more than 5,000 measurements involving multiple operators and instruments. The datasets include more than 20 samples (in replicate) and this number is likely to grow rapidly as their kits have recently been commercialized with analytical validation at 0.1% LOD achieved at 90% sensitivity, 98.4% specificity and high reproducibility.
University of Chicago
The University of Chicago's Center for Data Intensive Science (CDIS), in collaboration with the Open Commons Consortium (OCC) commits to organizing and operating an open Blood Profiling Atlas Commons. The Commons will be based upon the same open source software stack used by the NCI Genomic Data Commons so that the genomic, image and clinical data in the Commons can be shared with the appropriate security, privacy and compliance controls. To facilitate the rapid development of this critical resource, the OCC / University of Chicago team will contribute up to six months of engineering, bioinformatics and project management resources to the project and up to $500,000 of compute and storage resources for building the commons and for the use of the commons by the research community.
University of Michigan
The research teams of Muneesh Tewari, Daniel Hayes, Scott Tomlins and Todd Morgan at the University of Michigan (UM) provide their enthusiastic support for the Blood Profiling Atlas. They will share droplet digital PCR data from a comparison of multiple specimen collection tubes for stability of plasma cell- free tumor DNA over time, plasma whole genome sequencing data from up to 30 patients with advanced cancer, plasma cell-free RNA next generation sequencing data from up to 100 individuals as it becomes available in the coming year, and potentially circulating tumor cell enumeration and phenotype data from up to 100 patients with solid tumors. They will also share standard operating procedures for blood specimen collection and processing for cell-free DNA and RNA, experience in longitudinal blood sample collection, and expertise in generation and bioinformatic analysis of plasma cell-free RNA sequencing data. UM research teams will collectively commit up to $100,000 in investigative personnel, laboratory, bioinformatics and clinical research resources for activities contributing to the Cancer Moonshot Blood Profiling Atlas in the coming year.
University of Southern California
The Kuhn Laboratory at the University of Southern California commits to sharing data from the High-Definition Single Cell Analysis (HD -SCA) for the Blood Profiling Atlas on circulating tumor cell morphology, genomics and proteomics with simultaneous cell-free genomics on over 100 patients with breast cancer. Both cell-based and cell-free analyses are derived from the same blood sample and provide an initial concept for the Blood Profiling Atlas design. They will also share the visualization tools and infrastructure of the HD-SCA with the Open Commons Consortium to support the utilization of the Blood Profiling Atlas. They will also share clinical protocols and results from all pre-analytical variables and validation studies of the HD-SCA to support design of future Blood Profiling Atlas studies.
The Weill Cornell Medical Center
The research team of Dan Landau laboratory at Weill Cornell Medicine (WCM) and the New York Genome Center (NYGC) will provide their enthusiastic support for the Blood Profiling Atlas. They will share cell free tumor DNA data over time, from over 100 samples from patients with lung cancer and chronic lymphocytic leukemia as it becomes available in the coming year. They will also share standard operating procedures for blood specimen collection and processing for cell-free DNA, experience in longitudinal blood sample collection, and expertise in analytic innovation of plasma cell-free DNA sequencing data for the minimal residual disease and early detection setting. We are further committed to submit additional data in the future as it becomes available from our growing liquid biopsy initiative. The Landau research teams will collectively commit up to $200,000 in investigative personnel, laboratory, bioinformatics and clinical research resources for activities contributing to BloodPAC in the coming year.