Delivering the power of the world s most successful genomics platform

Transcription

1 Delivering the power of the world s most successful genomics platform

2 NextCODE Health is bringing the full power of the world s largest and most successful genomics platform to everyday clinical care NextCODE provides a comprehensive system to transform genomics data into medical understanding. We deliver fast, accurate, and actionable genomics insights to enable sequence-based diagnosis of diseases and improve patient care. Our system offers an automation standard that enables both public and private institutions to develop their best practices in bringing genetics into day-to-day medical use. Our integrated platform is designed for rapid mutation detection and clinical diagnostic applications using next-generation sequencing, novel bioinformatics, and proven data management technologies. INPUT PROCESSING RESULT Patient Samples GOR Database Architecture Big Data Solutions Mutation Discovery Sequence Miner for Deeper Analysis Clinical Grade NGS Legacy Patient Data Alignment & Variation Calling Genome Interpretation CSA System Dynamic & Scalable Data Storage & Retrieval Patient Data Management System Clinical Interface NextCODE Knowledge Base 40M validated variants annotated from >350K Whole Genomes, Curated Public Data Rapid Integration & Customization NextCODE Health offers an end-to-end solution for rapid patient diagnosis. 2 NextCODE Health

3 Our Platform: A Best-in-Class, End-to-End Solution for Rapid Mutation Detection Key Benefits A proven technology platform. Built over 16 years at decode genetics to meet the demands of datasets that are orders of magnitude larger than any found in public or private institutions, this unique platform has handled, analyzed, and stored whole genome sequence data from more than 350,000 individuals representing more than 40 million identified variants. In addition, the platform has proven scalability for storage and data queries, and has been used to power more than 350 original publications in gene discovery, diagnostics, and medical applications. An integrated system backed by decode s best practices. The system includes clinical nextgeneration sequencing, calibrated data analysis, effective genome interpretation, bioinformatics, and IT systems to enable the streamlined management of hundreds of thousands of patients from samples to mutation detection and confirmation. These solutions represent decode s best practices derived from successful genetic discoveries using linkage, genome-wide association, and next-generation sequencing. Reduce False Positives. We start from raw data, not VCF files, and run them using our analysis pipeline calibrated with data from thousands of whole genomes. This approach minimizes common alignment errors generated from other pipelines using sub-optimized parameters, resulting in significant reduction of false positives. Gain Clinical Insights on Cases without a Diagnosis. With 40 million validated variants to add to those in the public domain, we enable detection and confirmation of high-impact variants. NextCODE Knowledge Base 40 million validated variants annotated from >350,000 whole genomes 1.5 million indels and 6,600 loss-of-function mutations over 4,800 genes Variants with low allelic frequencies down to 0.01% Complements public databases, such as 1,000 Genomes or the NHLBI exome project. More samples and greater breadth and depth of sequence coverage. Our knowledge base enables users to quickly confirm rare mutations and filter out common variants that are unlikely to be high-impact disease variants. Rapid Confirmation. Our Genomic Ordered Relational (GOR) architecture facilitates instantaneous viewing of any candidate mutation at the sequence read level, increasing confidence via on-the-fly visual confirmation. Large-Scale Data Storage and Management. Raw data, analyzed data, and associated annotations can be stored in the GOR database tied to our Clinical Sequence Analyzer (CSA). No expensive hardware is required. Pay-As-You-Go Pricing. Our pricing is affordable, enabling you to analyze, interpret, store, and manage genomics data without the need to invest in internal IT infrastructure. 3

4 NextCODE s Comprehensive Products and Services Upstream: Sequencing NextCODE provides next-generation sequencing services through decode s CLIA-, CAP-, and ISO certified laboratory. These accreditations are an assurance of the highest sequencing data quality standards. We also provide a variety of competitively-priced next-generation sequencing services that do not require CLIA-grade sequencing. NextCODE provides clinical sequencing services through decode s CLIA-, CAP-, and ISO certified facility Mid-stream: Analysis NextCODE accepts legacy data from our clients. We use raw sequence read files for alignment and variant calling, which are calibrated for optimal results using the large cohorts sequenced by decode and NextCODE. Problematic calls are flagged or filtered leveraging our extensive knowledge of the unstable regions of the human genome. Benefits: Provides maximum yield of real variants by reducing both false positives and false negatives. Optimally-calibrated indel caller provides higher sensitivity and specificity. Tags or filters regions that are unstable to help users prioritize validation efforts. Enables instantaneous visualization of raw sequence data for confirmation of variants. Downstream: Genome Interpretation NextCODE s Clinical Sequence Analyzer (CSA) system enables users to quickly analyze their data through a clinically intuitive interface. The system operates on a petabyte scale using our GOR architecture, providing massively parallel ad hoc query and data analysis capabilities. Features: Custom candidate gene lists can be generated by users with phenotype-gene tools to complement the standard gene lists already included. Variant annotations can be stratified according to frequency, VEP class, predicted functional effects of missense variants, inheritance patterns, and effects on phenotypes, mortality, or expression. Potential pathogenic mutations are rapidly confirmed by an instant visualization of aligned sequence reads and cross-checked 4 NextCODE Health

5 with a continually updated, curated variation knowledge base made up of public domain, decode, and NextCODE data. User-friendly physician interfaces designed by clinicians enable users to manage their patient data, generate final reports, and notate diagnoses all within the same system, supporting the entire clinical team. Our CSA collaborative analysis features allow simultaneous access to patient sequence data by multiple users in real time, enabling sharing of analytical results, comments, and annotations. These features greatly facilitate collaborative genome interpretation where multiple users can create studies, and edit and share results and clinical reports within their institution or with collaborators around the world. Benefits: A clinically intuitive workflow enables users to rapidly analyze genomes, exomes, or transcriptomes, leading to de novo and rare mutation detection. Instantaneous visualization of raw sequence reads. This example shows that by hitting the Father BAM button, the NextCODE Genome Browser instantaneously loads BAM sequences enabling users to check the assembly and variant calls between the affected patient and the father. This detailed display of raw reads provides rapid visual confirmation that the father is a heterozygous carrier of the mutant C and his affected child is homozygous for the mutation. Similar analysis can be done for other members of the family and even for large cohorts. 5

6 NextCODE s Bigger Data Solutions Meeting the Big Data Challenge: The NextCODE Genomic Ordered Relational (GOR) Architecture Unlike other sequence analysis solutions, the NextCODE informatics systems have already been successfully used to manage sequence variation data for hundreds of thousands of individuals. Central to this capability is the unique design of the NextCODE GOR architecture and database. Instead of creating multiple data silos, the GOR architecture greatly simplifies the comparisons of variation data across large sets of patients with similar signs and symptoms, thereby leveraging the diagnostic power in the future avalanche of variation data generated by next-gen sequencing technologies. Equally important, our GOR database enables clients to dynamically retrieve, edit, and annotate their sequencing data on-the-fly without the common issues of substantial time-lag in retrieving and storing of data. Plus, user annotations on sequence variants from any given patient can be leveraged in the analysis of subsequent patients. Coupled with our web-based CSA system, our solution enables individual investigators and institutions to meet the challenge of managing big data without developing substantial IT infrastructure. Accelerating In-House Development: Rapid Integrations NextCODE provides an informatics infrastructure that allows medical centers to leverage their institutional experience and expertise in clinical genetics. It is our goal to enable in-house bioinformatics and IT efforts to take advantage of our advanced informatics platform. For example, experienced users and bioinformaticians can create their own data mining and analysis scripts, and deploy them to their own end users via our Sequence Miner tool. Also, our GOR database and data security design can be integrated to manage in-house data. Benefits: With the GOR database, clients can store and manage large amounts of raw and analyzed data at very affordable levels without the need to develop extensive IT infrastructure. NextCODE components and capabilities can easily be integrated into existing systems to enable internal development of best practices adopted at each institution. NextCODE s professional services team will provide consultations upon request. 6 NextCODE Health

7 Specifications Upstream: Sequencing NextCODE provides sequencing services Sample Submission Requirements: 2 ug of genomics DNA for exome and whole genome sequencing 3 ug to 4 ug of total RNA for transcriptome sequencing Minimal concentration 100 ng/ul - OR - NextCODE begins with client legacy data Data Submission Formats: FASTQ file Sample manifest file Mid-stream: Analysis NextCODE calibrated alignment and variation calling algorithms Calibrated indel caller provides higher sensitivity and specificity VEP variation effect prediction analysis based on gene context Missense mutation functional predictions Unstable region tagging or filtering Allelic frequencies, phenotype associations, and other variant annotations based on the NextCODE Knowledge Base, which includes both proprietary and public data Downstream: Interpretation and Data Management Informatics systems A. NextCODE data analysis and CSA system Sequencing quality control report Candidate gene report Report listing all known variations A report to identify putative pathogenic variants including: Autosomal dominant Autosomal recessive Autosomal compound heterozygosity X-linked recessive De novo variants B. NextCODE Genome Browser for data visualization C. NextCODE Sequence Miner for advanced sequence analysis and data mining D. Collaborative genome analysis workflow E. Clinical summary report Data Storage using NextCODE GOR Architecture and Database A. Data storage in NextCODE cloud- or serverbased hosting services B. Secondary analysis data is stored using BAM, VCF, and GOR formats C. Tertiary analysis is generated in GOR format and can easily be viewed or downloaded Recommended Computer Requirements CSA browser-based components require minimal computer resources for optimal performance NextCODE Genome Browser and NextCODE Sequence Miner, embedded in the CSA system, are Java Web Start modules which require 3Gb minimum memory for ideal performance NextCODE supports Windows, Linux, and Macbased operating systems 7

8 There s big data, and then there s bigger data We combine state-of-the-art sequencing and analytics with the world s largest genomics and phenotypic library. To learn more contact info@nextcode.com NextCODE Health One Broadway, 14 th Floor Cambridge, MA NextCODE Clinical Sequence Analyzer, NextCODE Genome Browser, NextCODE Sequence Miner, NextCODE GOR Architecture, and NextCODE GOR Database are registered trademarks of NextCODE Health.