Statement_of_Work_edited_12-31-15.doc

Draft Statement of Work (SOW) The Clinical Proteomics Tumor Analysis Consortium (CPTAC) Data Coordinating Center (DCC) 1 General Background

The overall objective of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) is to improve our understanding of cancer biology by conducting proteogenomic analysis on selected cancer types (up to 10 cancer types, 200 cases each; see Tumor Types of Interest) where unanswered questions remain about the molecular biology of the disease. This analysis will add a complementary layer of protein molecular biology that facilitates refinement of driver genes, enhance understanding of the pathogenesis through proteomic subtyping, and illuminate dynamic alterations in post translational modifications responsible for the dysregulation of cancer signaling networks and pathways.

The purpose of the CPTAC DCC is to collect, analyze, review, store, and distribute the data associated with CPTAC.

The CPTAC project involves several components, including:

· MultipleTissue Source Sites (TSS)

· 2 Biospecimen Core Resource (BCR)

· Genome Characterization Center (GCC)

· Quality Management System (QMS)

· Operations and Technical Support , Comprehensive Data Resource (NCI-OTS CDR)

· Several Proteome Characterization Centers (PCC)

· Several Proteogenomic Data Analysis Centers (PGDAC)

· Several Proteogenomic Translational Research Centers (PTRC)

· Data Coordinating Center (DCC)

The pipeline of these components will supply high-quality biospecimens and/or data to a network of Proteome Characterization Centers (PCC), Proteogenomic Translational Research Centers (PTRCs), and Proteogenomic Data Analysis Centers (PGDACs). Ultimately, the samples will be characterized for copy number variation, single nucleotide polymorphisms, DNA, RNA, and protein expression including variants and/or post-translational modification analysis. De-identified data will be made available through the CPTAC DCC and other NIH data resources. Overall quality for the entire project will be the responsibility of the QMS.

Heretofore, the PCCs, PGDACs, PTRCs, BCRs, CDR, and GCC will be referred to as CPTAC data generators.

Tumor Types of Interest:

1. Thoracic: Non-Small Cell Lung Carcinoma (Lung Adenocarcinoma)

2. Gastrointestinal: Pancreatic Ductal Adenocarcinoma (PDA)

3. CNS: Glioblastoma Multiforme (GBM)

4. Hematologic: Acute Myeloid Leukemia (AML)

5. Urologic: Clear Cell Renal Cell Carcinoma (ccRCC)

6. Head And Neck: Head And Neck Squamous Cell Carcinoma (HNSCC)

7. Skin: Cutaneous Melanoma

8. Soft Tissue: Sarcomas

9. Thoracic: Lung Squamous Cell Carcinoma (SQCC)

10. Gynecologic: Uterine Corpus Endometrial Carcinoma (UCEC) 2 Scope of Work

Independently, and not as an agent of the Government, the Contractor shall perform the services described below. The Contractor shall provide qualified personnel, material, equipment, and facilities not otherwise provided by the Government during performance of this contract.

The scope of this SOW is to adapt, develop, and support the CPTAC data coordinating center and data portals. Over the next five years, 6-10 tumor types will be characterized by the CPTAC components using a variety of platforms and experimental approaches to molecularly characterize cancer cells.

The Contractor shall furnish the necessary professional service experts to create and support the activities of the CPTAC DCC.

· The Contractor shall provide professional services in support of the CPTAC DCC. These services shall be performed with input from and in conjunction with NCI program management staff, the Contracting Officer’s Representative (COR), and with representatives from PCCs, PGDACs, PTRCs, BCRs, QMS, GCC, and CDR.

· The Contractor shall acquire data, code, documentation, and other necessary material from the previous DCC contractor.

· The Contractor shall work with the COR and representatives from other CPTAC program components to establish and execute program-wide procedures for data transmission, quality assurance checks, compliance with requirements for adoption of data standards, and other requirements related to the management, processing, aggregation, and distribution of CPTAC data.

· The Contractor shall establish and maintain a Common Data Analysis Pipeline for CPTAC proteomic and genomic data.

· The Contractor staff shall identify issues, conduct discussions, perform analyses, make recommendations, forge consensus, produce documentation, implement processes, and use their skills to achieve the Objectives of this SOW.

The Contractor shall provide experts with the following levels of expertise: PhD or equivalent-level knowledge and at least one person with five years past experience with life science data analysis and management, including data from patient demography and clinical annotations, pathology, proteomics, and genomics; at least one person with five years experience with high throughput methods for data processing, quality analysis and compliance with data standards; at least one person with five years experience in the management and analysis of tissue specimen, genomic, and proteomic data.

The Contractor shall provide software engineering and biomedical informatics support as described by Section 5 (Tasks to be Performed). The scope of this work includes the following types of activities:

· Professional services in support of the CPTAC DCC and data portal

· Requirements gathering and analyses

· High- and low-level systems architecture and design

· Database development services

· Project management

· Documentation of software, data model, and file structures

· Data analysis pipeline development and deployment

· Software testing

· Deployment

· Post-deployment on-going support

· Data transfer

· Data curation

· Development and maintenance of common data analysis pipeline for genomic and proteomic data

· Data monitoring with quality metrics

The Contractor shall aggregate all biomedical CPTAC data into a public resource that is accessible through a web interface developed and maintained by the contractor. The Contractor shall publicly release genomic and proteomic characterization data through NCI’s Genomic Data Commons.

3 Objectives This statement of work (SOW) shall meet the following major objectives:

· Adapt, design, build, specify, enhance, test, deploy, and support the CPTAC DCC, targeted to centrally store and/or coordinate data produced by the CPTAC data producers, and, with the CDR and QMS, coordinate genomic, proteomic, biospecimen, and clinical data on corresponding samples.

· Establish and execute standard operating procedures (SOP) for data transmission from CPTAC data producers to the DCC. SOPs will be developed in collaboration with representatives from these CPTAC data producers. The DCC will play a coordinating role among various CPTAC data producers generating similar data, and, along with the government COR, will be the final arbiter for definition of standard formats.

· Design and implement data analysis procedures that perform quality checks on incoming data and report anomalies and non-conforming data to the data producers and the QMS.

· Train a representative from each CPTAC data producer with appropriate SOPs for data transmission, and procedures for addressing non-conforming data.

· Implement a data management pipeline to process data and prepare it for public distribution in formats and systems compatible with the Database for Genotypes and Phenotypes (DbGaP) and NCI’s Genomic Data Cloud (GDC).

· Design, build, specify, enhance, test, deploy, and support the CPTAC Data Analysis Pipeline (CDAP) to provide a first level analysis of all CPTAC proteomic and genomic data. The pipeline shall analyze raw data through genomic sequence alignment and protein (gene) assembly.

· Post the data to the publicly accessible distribution points after quality checks and processing are completed such that NCI’s data release policy guidelines have been followed and cleared. Genomic and proteomic data shall be deposited to NCI’s Genomic Data Commons and any additional location required by NIH policy.

· Design, build, specify, enhance, test, deploy and support the CPTAC Data Portal, targeted to basic and clinical researchers, for browsing and downloading subsets of data that are selected based upon various characteristics of data provenance, source, and content. The CPTAC Data Portal shall display data from the CPTAC project and other sources.

· Design, build, specify, enhance, test, deploy and support the CPTAC Assay Portal, targeted to basic and clinical researchers, for browsing and downloading data related to targeted protein assays. The CPTAC Assay Portal shall display data from the CPTAC project and other sources.

· Provide regular and detailed reports of the status of CPTAC data, data quality, and data usage at all stages of the data management pipeline.

4 Technical Description

4.1 CPTAC Workflow

The CPTAC program has a general workflow of tissue accrual to data generation. The workflow has many steps and generates terabytes of data from clinical and research centers all over the country. The next two paragraphs briefly describe the data flow for the purpose of highlighting the necessity for a DCC.

Tissue Source Sites (TSSs) provide biospecimens (tumor and normal) to the Biospecimen Core Resource (BCR). The BCR is responsible for quality control (QC) prior to accepting the samples, and once accepted becomes the steward of the biological material and the subsequent derivative reagents. Tissue Source Sites submit corresponding clinical metadata to the Comprehensive Data Resource (CDR). The CDR aggregates clinical metadata with biospecimen data from the BCR. The BCR prepares the samples for proteomic and genomic analysis for the Proteome Characterization Centers (PCCs) and a Genome Characterization Center (GCC). The GCC and PCCs produce an immense amount of digital information about the cancer and normal samples, which are promptly transferred to the Data Coordinating Center (DCC). The DCC performs quality control and data analysis on these data. The DCC transfers the genomic data to either the NCI’s Genomic Data Commons or the National Center for Biotechnology Information (NCBI), both of which are able to host and distribute genome sequence data. The DCC hosts proteomic and other data via the CPTAC Data Portal. From here, the data are available for download by the public, but are further analyzed by the Proteogenomic Data Analysis Centers (PGDAC). Analyzed data are then uploaded to another partition of the DCC data servers and are also made available to the general public. Given the nature of the associated clinical metadata, some information is considered personally identifiable information (PII) and is protected behind a secure firewall, as required by the Health Insurance Portability and Accountability Act (HIPAA) of 1996. The QMS will ensure quality compliance and track and report conforming and non-conforming data along the CPTAC pipeline.

The CPTAC Assay Portal (https://assays.cancer.gov) serves as a public repository of well-characterized, targeted proteomic assays and is maintained by the DCC. The Assay Portal contains analytically validated assays and standard operating protocols (SOPs) that can be used to compare results across experiments, labs, and time. This, in turn, provides a common ground for clinicians, systems biologists and analytical chemists to facilitate widespread adoption of targeted assays, including mass spectrometry (MS)-based assays by disseminating SOPs, reagents, and assay characterization data. The current assay portal contains over 800 assays, generated primarily by CPTAC2 PCCs. Future assays will be transferred to the DCC by CPTAC3 PCCs, PTRCs, and the biomedical research community at large.

The DCC will serve an integral role in the CPTAC program as it will coordinate the data transfer for the PCCs, PGDACs, PTRCs, and GCC as well as monitor data quality for proteomic and genomic data. The DCC will primarily receive data from the PCCs, GCC, and CDR. The CPTAC Data Portal will likely provide links to several data analysis tools developed by the PGDACs. The DCC may host and/or analyze data from the PTRCs as well.

4.2 CPTAC Data coordinating center

Two categories of software are anticipated to be needed to carry out the CPTAC DCC tasks in this SOW. The first category includes scripts and programs to support data receipt, processing, analysis, and transformation, quality checks, and reporting. The Contractor shall reuse existing public scripts, programs, and software tools to carry out these functions, and develop new scripts, programs, and tools as needed.

Any CPTAC DCC related software developed with funding under this contract shall be released under an open-source license.

4.3 CPTAC Portals

The second category of CPTAC DCC related software includes data management systems to support public access to the data after it has been fully processed by the DCC. The contractor is encouraged to build on existing systems as use of entirely new software systems in this category are not in scope for this SOW.

The Contractor shall design, develop, build, and maintain the CPTAC Data Portal and the CPTAC Assay Portal. The Contractor shall maintain a detailed specification of the CPTAC Portals’ functionality as outlined below. The following is a high-level description of an example of the data types and functions to be supported by the Portal.

4.3.1 CPTAC Data Portal

4.3.1.1 CPTAC Data Portal Data Types

CPTAC shall generate several kinds of data including but not limited to the following: global protein identification, targeted protein quantification, analysis of specific types of post-translationally modified proteins, protein-protein interaction, exome sequencing, mRNA and miRNA sequencing, copy number variation, SNParray, genotyping, and epigenetic analysis.

For each of the platforms used by CPTAC investigators, the CPTAC data producers shall produce several levels of data, including but not limited to the following:

· Raw data: primary-level data directly from the instrument for a single sample, not compiled across samples, and not interpreted for the presence or absence of specific proteins or features. Examples: raw mass spectrum file; raw sequencing files (BAM); raw reads (FASTQ).

· Processed data: data for single samples that has been processed using software to identify and examine features, such as:

· Total ion current chromatograms

· Peptide peak lists and their associated intensities

· Protein identifications from single samples or fractions (Example: Proteins identified from a single HPLC fraction)

· Compiled protein identifications from multiple samples or fractions (Example: A list of the total proteins compiled from proteins identified from multiple HPLC fractions, or a comparison of the proteins identified from different biospecimens)

· Processed sequencing files (BAM)

· Cleaned reads (FASTQ)

· Alignments (SAM/BAM)

· Variations (VCF)

· Genome (FASTA)

· Genome annotations (GFF/BED)

· Analyzed data: Processed data which has been further analyzed in order to identify and examine features, such as:

· Post-translational modification analysis of proteins (Examples: phosphorylation or glycosylation)

· Analysis of protein-protein interactions (Example: antibody/antigen binding)

· Quantitative/Semi-quantitative analyses of proteins, post-translational modifications, and protein-protein interactions

· A comparison of all of the above analyses across different biospecimens of the same and differing types

· Summary finding: a quantified association, across classes of samples, among two or more specific proteins, features, sample characteristics, or clinical variables. Example: a finding that a particular protein or post-translational modifications of a protein is found to be amplified in 80% of a specific tumor type.

All data shall be linked to other data sources such as the clinical and other genomic, epigenomic, and expression analysis sources.

Datasets to be hosted on the CPTAC Data Portal include proteomic datasets from CPTAC 1 data (1 TB), CPTAC2 data (up to 15 TB), and CPTAC 3 (up to 50 TB).

4.3.1.2 Functions to be Supported by the CPTAC Data Portal

The Portal shall support at least the following four generic usage scenarios:

1. Provide a high level summary of the data that exist in the Portal (tumor types, data types, etc.), the progress of data release for a given tumor type, portal functions accessible to the public, caveats about data that may have been modified and/or redacted, and a user friendly means to assist in data navigation.

2. Support generation of reports on the status of data within the DCC. Reporting should allow for multiple views and inform different audiences:

· Multiple views may include:

· Time series of data transfer into and out of the DCC

· Modifications of data due to incomplete information or inability to meet quality metrics

· Workflow tracking of data associated with a single specimen

· Progress toward program goals aligned with tumor types

· Support for multiple audiences may include:

· CPTAC Management

· QMS Requirements (to be specified)

· Individual CPTAC Data Producers

· Basic researchers

· Clinical researchers

3. Provide a means to generate multiple views of the data to users, based upon a variety of possible characteristics of selection, using variables that are intrinsic to the data – absent of calculation and biological or clinical correlation.

· View raw and processed data for a given assay for a single sample.

· View raw and processed data for a given assay for a set of samples.

· View proteomic and genomic data for a single sample.

· View proteomic and genomic data for a set of samples.

· Download all raw data (by disease, data type, platform, CPTAC data producer)

· Facilitate access to PGDAC computational tools through various means such as: URL listed on the Data Portal, hosting the tool on the Data Portal, helping to develop a GUI between the Data Portal and the computational tool

4. Facilitate data quality assessment and review of raw and processed data

· Develop a workflow or process that integrates consistent and regular data quality checks.

· Example: As data are sent to the DCC, an example workflow might articulate steps for data acceptance, data integration into the DCC database, database value checks, database comparison to original data, and regular data quality assurance checks over time to minimize data corruption.

Regular reporting of these tasks and their results, periodicity, and format to be decided by the Contractor and the NCI COR, shall be necessary to effectively manage the DCC data systems.

Some CPTAC Data will be restricted to registered users. As part of this SOW, the Contractor shall implement appropriate access controls for the DCC and the Portal.

4.3.2 CPTAC Assay Portal

The CPTAC Assay Portal (https://assays.cancer.gov) serves as a public repository of well-characterized, targeted proteomic assays. The Assay Portal contains analytically validated assays and standard operating protocols that can be used to compare results across the board. This, in turn, provides a common ground for clinicians, systems biologists and analytical chemists to facilitate widespread adoption of targeted proteomic assays, such as mass spectrometry (MS)-based assays, by disseminating SOPs, reagents and assay characterization data.

Features:

· The CPTAC Assay Portal enables query of a database of well-characterized, targeted MS-based assays

· Bioinformatic annotations are pulled from outside sources to enable biologically relevant queries, as well as mapping of peptide analytes relative to sequence domains, isoforms, coding polymorphisms and post-translational modifications.

· The assay database is tied to Panorama, an open-source platform allowing for efficient collection and sharing of proteomics data in a vendor neutral format (for example, currently supporting data from six vendors: AB SCIEX, Agilent, Bruker, Shimadzu, Thermo and Waters), facilitating upload and viewing of assay characterization data, and download of Skyline documents for implementing the assays.

The CPTAC Assay Portal is organized into four levels:

· Level 1: is the landing page, which is designed to be relevant to biologists, enabling database query for validated assays to quantify proteins involved in specific cellular pathways or protein complexes, proteins whose genes map to specific chromosomal regions or proteins associated with specified Gene Ontology terms.

· Level 2: displays a protein-centric view onto which the positions of assay peptide analytes are mapped relative to features of interest, such as sequence domains, isoforms, coding polymorphisms and PTM.

· Level 3: provides detailed assay characterization data (accessible through Panorama https://panoramaweb.org/), allowing users to evaluate the expected analytical performance of each assay.

Assay characterization is a set of experiments designed to help users evaluate assay performance. There are five recommended experiments. Experiments 1 and 2 are required for each assay; while experiments 3–5 are optional for uploading to the CPTAC Assay Portal. Assays are entered through a web-based entry form and the uploading of data to Panorama. Characterization experiments are analyzed by scripts available through Panorama. Uploaded assays are subjected to manual review by site administrators to ensure data quality and the fulfillment of minimum requirements for assay characterization.

· Experiment 1 is a response curve designed to evaluate linearity, the within-batch precision of the liquid chromatography–MRM-MS analysis of the analyte peptide in a complex mixture and the upper and lower limits of quantification, and to provide data on selectivity.

· Experiment 2 determines the repeatability of measurements at multiple concentrations across 5 days.

· Experiment 3 tests selectivity by evaluating parallelism in multiple biological replicates of the matrix of interest.

· Experiment 4 evaluates the stability of peptides after sample preparation and helps the downstream user determine whether peptides can be left on the autosampler for a period of time or frozen before analysis.

· Experiment 5 aims to demonstrate that endogenous peptides can be quantified in a relevant matrix.

· Level 4: is designed to enable users to implement the assays in their laboratories. Users have the ability to download Skyline (a freely available Windows client application for building and analyzing targeted MS data) documents for assay implementation on most mass spectrometer platforms. For each assay, an SOP describing sample preparation and analysis is available for download, and a discussion board is provided for community-based information exchange on assay performance.

The portal currently contains over 800 assays, and CPTAC plans to add several hundred more assays each year. Additionally, the portal shall be able to receive contributions from the biomedical research community at large. Of note, the portal is able to accept data from a variety of assay types, targeted MS methods and reference targeted data, such as parallel reaction monitoring (PRM), MRM with high resolution (MRM-HR) and standard metrics such as iRT peptides, providing a versatile repository of well-characterized assays. As requested by the COR, the DCC shall add new features and tools to the portal to address needs of the program or biomedical research community.

5 Tasks to be Performed

The Contractor shall be responsible for ensuring the accuracy, timeliness, and completeness of all tasks performed under this effort.

Task 1 - Project Management

Project Management Plan

The Contractor shall develop a Project Management Plan (PMP) describing the means to accomplish project objectives. The PMP shall describe the technical approach, deliverables, methods for producing deliverables and the following management plans:

· Scope Management – scope definition; work breakdown structure (WBS) - encompassing planning, tracking, execution, and completion activities for all tasks; and change control.

· Data source management – activities to manage interactions with and between the various CPTAC data producers and the potentially un-harmonized formats of the data those data producers shall deliver to the DCC.

· Time Management – Outline activities, methods for producing deliverables, resource requirements, project durations and schedules, and project schedule controls. If an agile development process is to be employed, the activity sequencing of development sprints may be outlined here.

· Quality Management – quality assurance processes and controls; deliverable validation.

· Communications Management – stakeholder management and performance reporting. Given the large number of stakeholders and participants in CPTAC, the NCI COR and the Contractor shall agree upon an appropriate communications burden and process for the DCC Contractor.

· Risk Management – risk identification and management processes – to include a risk register to facilitate, monitor, and manage risks, as well as the communication of the status of risk prevention, mitigation, and response.

· Procurement Management – process for major purchases and acquisitions, such as the purchase of licenses and support for large information management systems.

· Change Management – address the inclusion of new data types from new and improved platforms put into use as CPTAC progresses, and to address how data will be forward-migrated over the course of the project.

The PMP shall include an MS Project formatted document including the WBS, and MS Word documents describing the other plans listed above. The draft WBS shall encompass any milestone reviews described in this SOW, as well as any requested Contractor supplied dates for Deliverables. Based on review of the PMP, the NCI COR shall provide approval to move forward on planned activities. The Contractor shall request prior approval for all activities not included in the PMP or any modifications to the plan after approval has been given. The final PMP, including all approved changes, shall be submitted as a deliverable at the end of the project.

Quarterly Status Reports

The Contractor shall document technical and financial status in detailed Quarterly Status Reports. All quarterly technical and financial reports shall be delivered in the template format provided by the COR during the project kickoff meeting. An acceptable Quarterly Status Report (QSR) format will be decided upon by the NCI COR and the Contractor. An anticipated QSR shall include the following:

· Program status overview, including status of deliverables/milestones.

· Description of activities completed during the quarter.

· Description of activities planned for the next quarter.

· Description of resolution(s) to previously – identified issues/obstacles.

· Delineation of risk factors that may delay completion of planned items and recommended solution(s).

· Budgeted total and budgeted quarterly hours vs. actual quarterly and total hours.

· Planned Value, Earned Value, and Actual Costs for the quarter and project.

· Estimated Cost to Completion.

· Task/Cost variance (for >10% variance include explanation/analysis).

· Other direct cost (ODC) progress/costs.

In addition, the Contractor shall provide status teleconferences with the NCI COR and the point of contact from CBIIT. These teleconferences will generally be held at a weekly frequency, but focused status teleconferences to address specific issues may also be requested by the NCI COR.

Final Project Summary Report and Project Close Out

The Contractor shall submit a Final Project Summary Report at the conclusion of the contract. This report shall describe the work accomplished, issues encountered and resolutions to them, recommendations for future enhancements, potential implementation strategies, inventory of the data files, and lessons learned. In combination with the final software code, documentation, and data files, this report shall provide the necessary information to operate the DCC and portal. The final version of the project summary report, including any approved changes made during review, shall be delivered to the COR in electronic form (Microsoft Word® format) at the completion of the project.

TASK 2 – System Requirements Gathering, Architecture, and Design

System and Software Requirements

The Contractor shall meet with individuals and groups representing major stakeholders and potential Portal users as determined by the Contractor and NCI COR, including the CPTAC data producers, CPTAC Program Staff representatives, and additional experts to be identified in order to develop the System Requirements. The Contractor shall summarize the requirements in a Software Requirements Specification (SRS) document. The SRS is a complete description of the behavior of the systems to be developed and shall explicitly state the functions and capabilities of the CPTAC Data coordinating center and Portal. The SRS shall contain the Data Producer, NCI, and CPTAC Requirements, Functional User Requirements, Non-functional Requirements, and Performance and Design Requirements.

Of significance to this task is the Functional User Requirements, which are largely comprised of the Use Cases. The Contractor shall develop a set of Use Cases specific to the intended use and operation of the systems, subsystems, and/or features to be developed. The set of Use Cases shall clearly identify how the system is intended to be used in its functional context. The System Use Cases shall make specific reference to any enterprise Use Cases described in the Technical Description, Objectives, and Scope of Work sections of this RFP document. In the event the Contractor employs an agile programming development process, User Stories and Epics may be substituted for Use Cases.

System and Software Design

The Contractor shall produce system and software architecture and design artifacts. Specifically, the Contractor shall submit a System and Software Design (SSD) document. The SSD document shall, at a minimum, describe the hardware and software architecture, and external interfaces.

The Contractor shall conduct and submit at least one (1) formal design review to the NCI COR. For iterative developments, after the initial design review, updates to the design documentation shall be completed and approved by the NCI COR before each planned increment.

The Contractor shall develop the Portal and shall develop the object model, data model, and data access methods to be used by the Portal. For any new objects, the Contractor shall annotate with Common Data Elements already in NCI’s Data Standards Repository (caDSR) or create new Common Data Elements according to CBIIT’s established process.

User interface design

The Contractor shall prepare a Portal site map and wire-frames for Portal pages. In preparing the user interface design, the Contractor shall consult with a usability-testing organization, which may be provided by the NCI.

Task 3 – deployment plan

Deployment Plan

The Contractor shall develop a Deployment Plan that outlines:

· The assumptions/dependencies/constraints of the system and the operational environment

· Operational readiness of the system. This shall include such items as a deployment diagram, site and environmental requirements, assessment of system readiness, product content, etc.

· The roll-out process – especially if it is a phased process

· Training requirements and expectations

· System documentation such as user manuals, data primers, system administration manual, etc.

· Transition to support

· Operations and maintenance planning

The Contractor shall execute the Deployment Plan and include the deployment activities within the testing protocols. The Deployment Plan shall include a successful deployment package for download by the public. A successful deployment for each release shall include a single, downloadable package, with a comprehensive System Administration guideline, and result in successful execution of the system executable files that function as prescribed in the system documentation. In the event the DCC software requires outside, third-party, open-source executable files, system requisites shall be clearly documented in the System Administration document.

Product Demonstration

The Contractor shall provide a Product demonstration as prescribed by the NCI COR . This shall be an end-user oriented demonstration of the product. In addition, if grid services are developed, a demonstration of all developed services, both data and analytical, shall be performed.

task 4 – domain model, data elements, and terminology selection and specification

In conjunction with the CPTAC BCR, PCCs, CDR, TSS, PGDAC, PTRC, and QMS components, the Contractor shall come to agreement on the standard vocabularies, data elements, and data models needed to represent data flowing to the DCC.

Working in concert with the CPTAC data producers, standard terminologies for annotations and representations shall be selected. Such terminology standards are expected to be drawn from the NCI Thesaurus, available from the NCI Enterprise Vocabulary Services (EVS, http://ncicb.nci.nih.gov/NCICB/infrastructure/cacore_overview/vocabulary). In cases where the NCI Thesaurus does not contain suitable terminology, sources from other redistributable terminologies hosted by NCI EVS or approved by the NCI COR and the Contractor, shall be used. Terminologies that are not hosted by NCI EVS or which have not been approved by the NCI COR shall not be selected for use in CPTAC. The DCC shall be responsible for executing these processes, and will receive support from caDSR and EVS staff as needed. The final selection of information models and corresponding registered data elements shall be documented and reported to all CPTAC Centers.

The following reports shall be submitted upon completion of each implementation phase:

· Report detailing information model for each category of data, accompanied with the models themselves in suitable file formats.

· Report detailing specific caDSR-registered data elements, to be used as the basis for specification of data processed and distributed by the DCC.

· Report detailing the terminology sources to be used for controlled vocabulary.

task 5 – system implementation

The Contractor shall develop software code to implement Portal functions and shall conduct unit and integration testing. In order to manage the development activities, the Contractor shall maintain a Product Backlog detailing the functions to be developed, priority of each function, and estimated development time per function. The Contractor shall review and assess the system’s testing and quality assurance procedures. Where existing open source software is available to perform a function, the Contractor shall adapt and use existing software rather than developing new software, unless there are compelling reasons to the contrary which must be approved by the NCI COR.

Task 6 – Quality assurance The Contractor shall conduct basic Quality Assurance (QA) testing on data that it receives from the CPTAC components. The DCC shall prepare a QA Test Plan for approval by the NCI COR. The DCC shall work with the QMS to report conforming and non-conforming data and compliance with the overall CPTAC Quality Manual. The QA Test Plan must address:

· Transmission integrity

· Data completeness

· Data validation

· Data quality metrics

· Reporting back to CPTAC data producers

· Reporting out to the CPTAC program staff and QMS Implementation:

The Contractor shall implement the QA plan within the DCC. The QA plan will be vetted by the NCI COR and shall be in compliance with the CPTAC Quality Management System.

Operation:

The Contractor shall conduct Quality Assurance as part of the DCC activities during the period of performance and maintain an up to date QA log.

Data Quality Non-conformities:

If the Contractor detects a systematic QA problem with one or more of the CPTAC data producers, it shall communicate this problem to the appropriate Center and maintain a record of the issue(s) within the QA log. The Contractor shall work with the identified Center to attempt to ascertain the cause of the problem and shall engage the Center to identify solutions. If, after three months, this activity proves ineffective, the Contractor shall notify the Government in writing that a Center is non-compliant.

task 7 – staff training

The Contractor shall ensure that all staff, including subcontractors and consultants, are properly trained in handling secure data and IT security. A staff training plan shall be developed and must be approved by the NCI COR and CPTAC Program staff before implementation of any staff training.

TAsk 8 – data collection and processing

Standard Operating Procedures (SOP).

The Contractor shall conduct a series of discussions with the CPTAC data producers and the QMS to define and establish appropriate Standard Operating Procedures for transmission and processing of data from the various data generation centers to the DCC. These SOPs shall address the following Tasks. It is expected that the current DCC SOP shall serve as the standard, and should be modified as appropriate.

Sample identification:

The Contractor shall obtain initial sample information from the BCR and maintain an index of sample identifications for the purpose of aggregating information from the various CPTAC components. This sample index shall be used to communicate CPTAC sample identifiers to all participating groups, and shall serve as the primary means to track sample and derivative data as it is generated and released through the CPTAC Portal and DCC.

Data Transfer Schedules:

The Contractor shall work with the CPTAC data producers to determine the appropriate schedules for transfer of information to the DCC, in accordance with the CPTAC data release policies. Genomic data release will be done in accordance with NIH data release policies.

Physical Mechanism of Transfer:

The Contractor shall define the procedures for the physical transmission of data (FTP, magnetic or optical media, cloud, etc.). As the CPTAC program undertakes production, transmission of data may become a real obstacle for adequate release and access of information. In some cases, institutions will need to access terabytes of information on a consistent basis. Understanding the information transfer needs of CPTAC and implementing an appropriate solution shall be a high priority of the Contractor.

Security:

The Contractor, in cooperation with the CPTAC data producers shall determine the appropriate level of security for the persistent data and during data transmission. This shall include cryptographic requirements (if any), secure transfer, etc. The Contractor shall create a process that is compatible with and in accordance with the terms of this contract, applicable Federal Information Security requirements (FISMA, HIPAA, 21CFR11, etc.) and the boundaries of the informed consent attached to the samples.

Quality Assurance/Validation:

The Contractor shall provide appropriate Quality Assurance (QA) checks and data validation. This requirement is described in more detail in Task 6.

Transformation:

The Contractor shall take the data feeds from the CPTAC components and provide them to repositories as directed by the NCI COR. The Contractor shall provide a procedure for supplying this data to data-persistence systems and repositories.

ETL

The Contractor shall develop and release Extract/Transform/Load (ETL) processes to load CPTAC data into data systems external to the DCC. In addition, the Contractor shall transform the data into convenient bulk downloads.

Reporting on Quality and Productivity Metrics

The Contractor shall provide metrics to the CPTAC program regarding data received from the CPTAC components. The report shall include identification of all data that fails QA checks and data validation. The report shall also include data completeness metrics, measured against cases, samples, and reporting Center. These reports shall be delivered at least monthly, not later than the last day of the month following the activity.

SOP Implementation:

Data processing script and software program adoption and development.

The Contractor shall identify all data processing and transformation software scripts and programs that are needed to support the SOPs defined in Task 8.1. This software is for internal use in the DCC. The Contractor shall first attempt to obtain data processing scripts and programs from public and open source bioinformatics resources. In cases where a need is not fulfilled by a public or open source software resource, after approved by the NCI Contracting Officer and COR the Contractor shall develop and test the scripts, using the most efficient programming technology suited to the task. All scripts and programs, whether adopted from external resources or developed by the Contractor, shall be tested and validated prior to use in production.

Implementation:

The Contractor shall implement the SOPs described in Task 8.1 and the associated processes for quality assurance and data persistence and distribution.

SOP Validation:

The Contractor shall provide a test plan for each SOP and conduct several tests of the data transfer mechanism. If problems are discovered, the Contractor shall modify the SOP and/or the underlying process to correct the problems.

Production:

The Contractor shall collect data from the CPTAC data producers during the contract period as described by the SOPs created and implemented in Tasks 8.1 and 8.2. The Contractor shall perform all required activities described by the SOPs and this SOW.

task 9 – data analysis The Contractor shall design, develop, adapt, build, specify, test, and deploy two (2) Common Data Analysis Pipelines (CDAP): one for genomics and one for proteomics. Each CDAP shall be applied to all respective genomic or proteomic data maintained at the DCC.

The Genomic CDAP shall address characterization and identification. Under characterization, the CDAP shall fully describe the genomic events, including somatic and germline events at the DNA and RNA levels, in tumor and normal samples coming from a single individual. Specific tasks shall include:

1. Estimating the purity/ploidy and absolute copy-number and mutation data

2. Pinpointing rearrangement breakpoints in sequencing data

3. Estimating contamination level in sequencing data

4. Identifying rearrangements in sequencing data

5. Detecting genomic segments of constant allele-specific copy-number based on array data

6. Identifying short insertions and deletions in sequencing data

7. Identifying point mutations in sequencing data

8. Detecting pathogenic sequences in sequencing data

9. Calculating QC metrics for RNA-seq data

10. Gene level digital expression for mRNA-seq data

11. Alternative splicing analysis for mRNA-seq data

12. Gene fusion analysis for mRNA-seq data

13. Detecting copy-number changes from sequencing data

Under interpretation, the CDAP shall analyze the characterization data across a set of individuals with the aim of identifying genes, regions, and pathways that are altered beyond what is expected by chance to identify subtypes of the disease. Specific tasks shall include:

1. Detecting regions of significant copy-number gains and losses

2. Detecting significantly mutated genes

3. Annotating human genomic point mutations and indels The Proteomic CDAP shall perform a basic characterization of all CPTAC proteomic data. Using raw mass spectra as its input, the CDAP shall:

1. Convert raw spectra to mzML and additional file types necessary for processing

2. Identify peptides from spectra

3. Provide quantitative information associated with identified peptides. This quantitative information may derive from a variety of quantitative methods including labelled and label-free methods.

4. Annotate peptide sequences with post-translational modifications, including phosphosite localization.

5. Calculate quality control metrics of data quality similar to pmid19837981.

6. Perform generalized parsimony to derive, from the identified peptides, an inventory of proteins and/or translated gene products. This protein inventory shall have a false discovery rate of 5% or less.

task 10 – CPTAC assay portal

Regarding the CPTAC Assay Portal, the Contractor shall:

1.

Receive current assay portal code and data previous Contractor 2.

Stand up assay portal to support the features listed in Section 4.3.2 3.

Maintain assay portal

4.

Enable assay portal to receive new data

5.

Perform quality control on new data in conjunction with manual review by site administrators (as specified by the NCI COR)

6.

Deploy new data from CPTAC data producers and the research community 7.

Implement new features and functionality tools to the assay portal as directed by the COR task 11 – data persistence and distribution

Plan for bulk data distributions on public FTP site.

As part of the SOPs, the Contractor shall develop plans for the uploading of bulk aggregated data files to the DCC anonymous FTP site. The Contractor shall design bulk data download formats. The plan shall provide for the immediate posting of all data that passes quality checks and shall not include data that fails quality checks, in accordance with the CPTAC data release policy. If data which have passed quality checks and have been posted are subsequently determined to not meet quality standards, then the Contractor shall immediately remove them from the FTP site and post an explanatory statement to the site.

task 12 – data use, disclosure, and handling of sensitive information

Security Controls

The contractor shall comply with the security controls stated in the contract.

Privacy Standards

The Contractor shall address the potential sensitivity of the information collected, information security issues, local Institutional Review Board (IRB) requirements and the Health Insurance Portability and Accountability Act (HIPAA) of 1996 in its design of the system in question.

Final regulations issued by the Department of Health and Human Services (DHHS) provide privacy and security standards that shall be observed in the handling of patient data resulting from biomedical research. HIPAA privacy standards shall be used to establish safeguards and restrictions for the use and disclosure of research records. HIPAA security standards shall be used to help cancer centers implement administrative, physical, and technical safeguards to protect electronic health information. Improper use or disclosure of sensitive information under the rules may be subject to criminal or civil sanctions prescribed in HIPAA.

task 13 – Documentation of software

If required by the NCI COR, the Contractor shall prepare the following documentation;

· Application Developers Guide

· System Administration Guide task 14 –Transition Plan

The Contractor shall develop software code to implement DCC and Portal functions and shall conduct unit and integration testing. In order to manage the development activities, the Contractor shall maintain a Product Backlog detailing the functions to be developed, function priority, and estimated development time per function. The Contractor shall coordinate with the Quality Management Systems Contractor and NCI COR, who will review and assess the DCC Contractor’s testing and quality assurance procedures. Where existing open source software is available to perform a function, the Contractor shall adapt and use existing software rather than developing new software, unless there are compelling reasons to the contrary which must be approved by the NCI COR and Contracting Officer.

At the conclusion of the period of performance, the Contractor shall deliver a final project management plan detailing the work accomplished over the course of the project. As directed by the COR, the Contractor shall provide to another contractor all data, code, documentation, and any other material necessary to stand up the CPTAC DCC and Portals.

6 Travel

It is expected that the Contractor will need to travel to the site of the CPTAC data producers (location(s) to be determined) on occasion during the requirements phase, and possibly later. CPTAC is expected to consist of eleven (11) to fifteen (15) data producers. Additionally, the Contractor shall attend the semi-annual CPTAC program meeting to be held near Bethesda, MD.

7 Deliverables

All Deliverables shall be submitted in accordance with Sections C., D., E., and F. of the contract and as outlined in the SOW.

7.1 Deliverable List and Due Dates

The following table contains a list of deliverables with notation of due dates.

Acceptance criteria for each of the primary deliverables are given below. Inspection and acceptance also will be performed in accordance with the terms of the contract under Section E. (The contract will state that acceptance is presumed within 30 calendar days unless notified in writing by the CO – standard language.)

Cross Project Deliverables