SSS_SOW RFI_SS.docx

Statement of Work / Performance Work Statement Title: Simulation Science Section (SSS) Analytics Services Period of performance of this contract is: August 2024 to July 2025 Base Period: August 2024 to July 2025

SECTION 1 – BACKGROUND

The Office of Innovation and Analytics (OIA) includes four sections, one of which is the Simulation Science Section (SSS).

The Office of Innovation & Analytics (OIA) collects, analyzes, and interprets data and disseminates scientific information to enable internal and external partners to make actionable decisions regarding exposure to hazardous substances. OIA provides analytical and modeling expertise, develops new analytical tools, and integrates geospatial science in public health activities.

The Simulation Science Section (SSS) develops and applies computer models to help find the best ways to evaluate and reduce the hazards of toxic chemicals. The group’s responsibilities include:

· Aiding evaluations of exposures to hazardous chemicals in communities

· Providing estimates of toxicity from exposure to chemicals in the environment and

· Contributing advice and support to help reduce the impacts of exposure to chemicals.

The scientists in the SSS support basic and applied research projects in collaboration with NCEH, government, and academic institutions. Collectively, these projects contribute to the goal of developing and using modeled estimates and expertise that help reduce the effects of toxic chemicals found in communities.

A current focus area is assessing the toxicity of environmental and emerging chemicals and modeling that can reveal various genetic changes linked to toxic chemical exposures. SSS staff have developed several toxicogenomics projects. Agency for Toxic Substances and Disease Registry is interested in assessing and predicting the ototoxicity of the environmental chemicals of their interest. This requires unique and valuable insight in this area and expertise with proprietary datasets. This will provide ATSDR with an overview of the existing knowledge about hearing loss causes, prioritize genes/proteins most relevant to hearing loss and with drug target potential, and reconstruct visual pathway maps describing molecular events in hearing loss. The prospective vendor is uniquely positioned to provide the following with a combination of proprietary data and analysts who are experts in data utilization of the proprietary products.

ATSDR and partners have used the prospective vendor’s exclusive licenses and have published and produced research findings using these licenses. Additional services the prospective vendor will provide are 1) Literature and dataset analysis using Drug Discovery Intelligence to determine Drugs and Targets relevant to the treatment of hearing loss Adverse Events; to determine drugs and targets reported to have hearing loss Adverse Events; and to create a custom list of chemicals and similar drugs associated with ototoxicity.

2) Prioritization of proteins most relevant to hearing loss. The data being leveraged in Item 1 will be used for bioinformatics work for pathway knowledge, network algorithms, and disease similarity approaches. In addition, the prospective vendor will assess the novelty of the identified targets using Competitive Intelligence for global coverage of diseases, drugs and biologics in active or inactive development. 3) Pathway map reconstruction. After data integration for Item 1&2, the prospective vendor will provide a detailed pathway map and adverse outcome pathway using Metabase.

The prospective vendor will assist OIA/SSS and ATSDR program staff with current computational toxicology predicting tools to help accomplish the agency's mission to investigate environmental exposures to hazardous substances in communities. The vendor will be used to develop and apply qualitative and quantitative models of several measures of toxicity endpoint. This will include a qualitative assessment of nuclear receptor toxicity in mammals.

The vendor’s scientific support will allow staff from SSS/OIA to deliver high-quality biological and toxicological systems content in context, giving essential data needs and analytics to accelerate scientific research.

SECTION 2 – PURPOSE/OBJECTIVE

This procurement will be used to examine, summarize, and interpret available toxicological and omics studies to ascertain levels of exposure for humans that may be associated with health effects.

Our studies and projects aim to provide the necessary and sufficient evidence to support a conclusion on a health effect through available data and computational predictions.

SECTION 3 – SCOPE OF WORK

The scope of work is for scientific service support for use in the Simulation Science Section (SSS).

The Agency for Toxic Substances and Disease Registry (ATSDR)/Simulation Science Section (SSS) presents and publishes its findings on scientific forums and journals for hazardous substances. At SSS, we examine, summarize, and interpret available toxicological and omics studies to ascertain human exposure levels that may be associated with health effects. Our studies and projects aim to provide the necessary and sufficient evidence to support a conclusion on a health effect through available data and computational predictions.

Many experts in the field use MetaCore and MetaDrug tools and services to assemble and analyze human biological and toxicological networks as a valuable method for the integration and functional interpretation of high- throughput experimental data. Many other partners and collaborators use these tools at research and federal agencies. OIA/SSS has been using their licenses, MetaCore and MetaDrug for over a decade; these tools now host data from several projects for OIA/SSS and our manuscripts data. MetaCore and MetaDrug are unique in their highly configurable software platform that allows customization and optimization. It has been approved and evaluated by our IT personnel.

Because MetaCore and MetaDrug are online platforms, it also allows for easy access and enhanced communication around workflow.

SECTION 4 – TASKS TO BE PERFORMED

Task 1: Literature and dataset analysis focused on the identification of drugs, genes, and proteins relevant to hearing loss The vendor shall search and curate various resources for lists of implicated genes and OMICs data (e.g., transcriptomics, proteomics, metabolomics) related to hearing loss. These resources may include Gene Expression Omnibus (GEO), Drug Discovery Intelligence (DDI) product ( genomic records, including genetic variants), OFF-X target safety database, as well as published literature and Science and public literature databases. The contractor shall download, process, and identify differentially abundant molecular entities in respective datasets and supply them to our Target Identification and pathway map reconstruction workflows. This includes:

a. Up to 3 public OMICs datasets relevant to hearing loss.

b. Custom list of chemicals and similar drugs associated with ototoxicity that could be mapped on Metabase

c. Drugs and Targets reported to have hearing loss Adverse Events [OFF-X]

d. Drugs and Targets relevant to the treatment of hearing-loss relevant conditions [DDI] Task 2: Target Identification for Hearing Loss Prioritization of proteins most relevant to hearing loss Modern methods of drug target identification involve different types of scientific information (disease biomarkers, protein interactions, pathway data, OMICs data) and advanced algorithms to find connections between genes or pathways and disease. The Analytics shall use a broad portfolio of methods based on:

· Approaches that use annotated data from knowledge bases

· Approaches that use various bioinformatics techniques to make accurate novel predictions.

In this project, the contractor shall employ both types of approaches to prioritize human (non- viral) targets for Hearing Loss. As a starting point, the contractor shall build molecular signatures from the datasets identified during step 1. Using those signatures as molecular descriptors of the disease, the contractor shall apply our target prioritization workflow. This employs 3 approaches (pathway knowledge, network algorithm, and disease similarity approaches), which will be combined into an integrated target score. The contractor shall then assess the novelty of the identified targets using analytics’ comprehensive competitive intelligence databases. As a project outcome, ATSDR will receive prioritized human targets for Hearing Loss and insights into the biological mechanisms underlying those targets in this indication, with some recommendations relevant to the selection of novel targets and drugs/chemicals affecting them.

Task 3: Pathway map reconstruction, based on Task 1 and 2:

a. Data Integration for steps 1 and 2 As a preparatory step for pathway map reconstruction, similar drugs and chemicals identified on steps 1 and 2 will be mapped and classified.

b. Detailed pathway map describing molecular events in hearing loss The pathway map shall be reconstructed based on the in-depth analysis of the literature and results of Steps 1 and 2 output. The list of identified drugs/ chemicals from Step 1 of the project with a known and curated target and MOA (according to MetaBase) will be mapped to the detailed reconstructed pathway map to highlight the MOA (Top 5 drugs per target will be represented on the map).

c. Adverse Outcome Pathway (AOP) The AOP represents a high-level schematic description of the cascade of key events (KEs) and key-event relationships (KERs) that underpins the link between a molecular initiating event (MIE) and an adverse outcome (AO), such as hearing loss. AOPs describe a functional or anatomical change at the cellular level resulting from the exposure of a living organism to a toxicant and evaluate the relevance of animal data. The drugs/ chemicals identified during Step 1 shall be classified into groups by the mechanism of action (MOA). The AOP shall be reconstructed taking into account one of the identified MOA of the group of drugs/ chemicals (as a POC, the contract shall propose to start with 1 MOA group for AOP reconstruction)

SECTION 5 – GOVERNMENT FURNISHED PROPERTY

NA

SECTION 6 – PLACE OF PERFORMANCE AND CONTRACT SUPPORT HOURS

NA

SECTION 7 – TRAVEL

NA

SECTION 8 – DELIVERABLES/REPORTING SCHEDULE

Deliverables, Fees and Timeline

Task

Deliverables Fees and Timeline

Task 1. Literature and dataset analysis

a. Public Omics Datasets review with recommendation on the most relevant dataset selection for further analysis (up to 3) (Excel)

b. Custom list of chemicals associated with ototoxicity with similar drugs that could be mapped on Metabase/IDs (Excel)

c. Drugs and Targets reported to have hearing loss Adverse Events [OFF-X] (Excel)

d. Drugs and Targets relevant to treatment of hearing- loss relevant conditions [DDI] (Excel)

~4 weeks after project kickoff

Task 2. Target Identification for hearing loss

a. Differentially expressed genes / proteins for each analysed dataset (up to 3), with fold changes and p- values (Excel)

b. Feature matrix used for Machine Learning model, including pathway knowledge-based scores, network algorithm-based scores and disease similarity-based scores for each candidate target relative to the indication of interest (Excel)

c. Integrated target prioritization (Excel)

d. Supporting evidence for target prioritization (html pages with imbedded tables and visualizations)

e. Report with detailed description of the target prioritization process and result (html)

~6 weeks after step 1 completion**

Task

Deliverables Fees and Timeline

f. Shortlist of up to 5 human targets

Task 3. Pathway map reconstruction

a. Detailed pathway map depicting molecular events in hearing loss as well as effect of selected chemicals and targets on them (png image file and Word document with the report describing the depictured mechanisms)

b. Adverse Outcome Pathway (AOP) for 1 MoA group with effects of selected chemicals on it (png image file and Word document) $___for detailed map and 1 AOPs, ~16 weeks after part 2 completion*

* -execution time potentially could be reduced by task parallelizing Timeline details Task 1. Literature and dataset curation focused on the identification of drugs, genes, and proteins relevant to hearing loss [ ~4 weeks after project kick-off] Task 2. Target Identification for hearing loss [~6 weeks after Step 1 completion**] Task 3. Pathway map reconstruction, based on Steps 1 and 2:

a. Detailed pathway map [~8 weeks after Step 2 completion]

b. Adverse Outcome Pathway (AOP) [~8 weeks per AOP after Step 3a completion]

** - excluding time spent by customer reviewing interim results and providing feedback on the target selection

The full project will last for 26 weeks from the project kick-off. The project will kick off within 2 weeks of the execution of SOW and include bi-weekly update calls to review the methodology and results.

SECTION 9 – REFERENCE MATERIALS

NA

SECTION 10 – MINIMUM VENDOR QUALIFICATIONS

NA

SECTION 11 – SPECIAL REQUIREMENTS

Electronic and Information Technology Accessibility Notice

(a) Section 508 of the Rehabilitation Act of 1973 (29 U.S.C. 794d), as amended by the Workforce Investment Act of 1998 and the Architectural and Transportation Barriers Compliance Board Electronic and Information (EIT) Accessibility Standards (36 CFR part 1194), require that when Federal agencies develop, procure, maintain, or use electronic and information technology, Federal employees with disabilities have access to and use of information and data that is comparable to the access and use by Federal employees who are not individuals with disabilities, unless an undue burden would be imposed on the agency. Section 508 also requires that individuals with disabilities, who are members of the public seeking information or services from a Federal agency, have access to and use of information and data that is comparable to that provided to the public who are not individuals with disabilities, unless an undue burden would be imposed on the agency.

(b) Accordingly, any offeror responding to this solicitation must comply with established HHS EIT accessibility standards. Information about Section 508 is available at http://www.hhs.gov/web/508. The complete text of the Section 508 Final Provisions can be accessed at http://www.access-board.gov/sec508/standards.htm.

(c) The Section 508 accessibility standards applicable to this contract are: 1194. 205 WCAG 2.0 Level A & AA Success Criteria 302 Functional Performance Criteria 502 Inoperability with Assistive Technology 503 Applications 504 Authoring Tools 602 Support Documentation 603 Support Services

In order to facilitate the Government's determination whether proposed EIT supplies meet applicable Section 508 accessibility standards, offerors must submit an HHS Section 508 Product Assessment Template, in accordance with its completion instructions. The purpose of the template is to assist HHS acquisition and program officials in determining whether proposed EIT supplies conform to applicable Section 508 accessibility standards. The template allows offerors or developers to self-evaluate their supplies and documentation detail - whether they conform to a specific Section 508 accessibility standard, and any underway remediation efforts addressing conformance issues. Instructions for preparing the HHS Section 508 Evaluation Template are available under Section 508 policy on the HHS Web site http://hhs.gov/web/508.

In order to facilitate the Government's determination whether proposed EIT services meet applicable Section 508 accessibility standards, offerors must provide enough information to assist the Government in determining that the EIT services conform to Section 508 accessibility standards, including any underway remediation efforts addressing conformance issues.

(d) Respondents to this solicitation must identify any exception to Section 508 requirements. If a offeror claims its supplies or services meet applicable Section 508 accessibility standards, and it is later determined by the Government, i.e., after award of a contract or order, that supplies or services delivered do not conform to the accessibility standards, remediation of the supplies or services to the level of conformance specified in the contract will be the responsibility of the Contractor at its expense.

(e) Electronic content must be accessible to HHS acceptance criteria. Checklist for various formats are available at http://508.hhs

Information Security and Privacy Safeguarding Information and Information Systems. In accordance with the Federal Information Processing Standards Publication (FIPS)199, Standards for Security Categorization of Federal Information and Information Systems, the Contractor (and/or any subcontractor) shall:

a. Protect government information and information systems in order to ensure: Confidentiality, which means preserving authorized restrictions on access and disclosure, based on the security terms found in this contract, including means for protecting personal privacy and proprietary information; Integrity, which means guarding against improper information modification or destruction, and ensuring information non-repudiation and authenticity; and Availability, which means ensuring timely and reliable access to and use of information.

b. Provide security for any Contractor systems, and information contained therein, connected to an HHS network or operated by the Contractor on behalf of HHS regardless of location. In addition, if new or unanticipated threats or hazards are discovered by either the agency or contractor, or if existing safeguards have ceased to function, the discoverer shall immediately, within one (1) hour or less, bring the situation to the attention of the other party.

c. Adopt and implement the policies, procedures, controls, and standards required by the HHS Information Security Program to ensure the confidentiality, integrity, and availability of government information and government information systems for which the Contractor is responsible under this contract or to which the Contractor may otherwise have access under this contract. Obtain the HHS Information Security Program security requirements, outlined in the HHS Information Security and Privacy Policy (IS2P), by contacting the CO/COR or emailing fisma@hhs.gov.

d. Comply with the Privacy Act requirements and tailor FAR clauses as needed.

Controlled Unclassified Information (CUI). CUI is defined as “information that laws, regulations, or Government-wide policies require to have safeguarding or dissemination controls, excluding classified information.” The Contractor (and/or any subcontractor) must comply with Executive Order 13556, Controlled Unclassified Information, (implemented at 3 CFR, part 2002) when handling CUI. 32 C.F.R. 2002.4(aa) As implemented the term “handling” refers to “…any use of CUI, including but not limited to marking, safeguarding, transporting, disseminating, reusing, and disposing of the information.” 81 Fed.

Reg. 63323. All sensitive information that has been identified as CUI by a regulation or statute, handled by this solicitation/contract, shall be:

a. marked appropriately;

b. disclosed to authorized personnel on a Need-To-Know basis;

c. protected in accordance with NIST SP 800-53, Security and Privacy Controls for Federal Information Systems and Organizations applicable baseline if handled by a Contractor system operated on behalf of the agency, or NIST SP 800-171, Protecting Controlled Unclassified Information in Nonfederal Information Systems and Organizations if handled by internal Contractor system; and

d. returned to HHS control, destroyed when no longer needed, or held until otherwise directed. Destruction of information and/or data shall be accomplished in accordance with NIST SP 800- 88, Guidelines for Media Sanitization.

Protection of Sensitive Information. For security purposes, information is or may be sensitive because it requires security to protect its confidentiality, integrity, and/or availability. The Contractor (and/or any subcontractor) shall protect all government information that is or may be sensitive in accordance with OMB Memorandum M-06-16, Protection of Sensitive Agency Information by securing it with a FIPS 140- 2 validated solution.

Confidentiality and Nondisclosure of Information. Any information provided to the contractor (and/or any subcontractor) by HHS or collected by the contractor on behalf of HHS shall be used only for the purpose of carrying out the provisions of this contract and shall not be disclosed or made known in any manner to any persons except as may be necessary in the performance of the contract. The Contractor assumes responsibility for protection of the confidentiality of Government records and shall ensure that all work performed by its employees and subcontractors shall be under the supervision of the Contractor. Each Contractor employee or any of its subcontractors to whom any HHS records may be made available or disclosed shall be notified in writing by the Contractor that information disclosed to such employee or subcontractor can be used only for that purpose and to the extent authorized herein. The confidentiality, integrity, and availability of such information shall be protected in accordance with HHS and CDC policies. Unauthorized disclosure of information will be subject to the HHS/CDC sanction policies and/or governed by the following laws and regulations:

a. 18 U.S.C. 641 (Criminal Code: Public Money, Property or Records);

b. 18 U.S.C. 1905 (Criminal Code: Disclosure of Confidential Information); and

c. 44 U.S.C. Chapter 35, Subchapter I (Paperwork Reduction Act).

Standard for Encryption. The Contractor (and/or any subcontractor) shall:

a. Comply with the HHS Standard for Encryption of Computing Devices and Information to prevent unauthorized access to government information.

b. Encrypt all sensitive federal data and information (i.e., PII, protected health information [PHI], proprietary information, etc.) in transit (i.e., email, network connections, etc.) and at rest (i.e., servers, storage devices, mobile devices, backup media, etc.) with FIPS 140-2 validated encryption solution.

c. Secure all devices (i.e.: desktops, laptops, mobile devices, etc.) that store and process government information and ensure devices meet HHS and CDC-specific encryption standard requirements. Maintain a complete and current inventory of all laptop computers, desktop computers, and other mobile devices and portable media that store or process sensitive government information

(including PII).

d. Verify that the encryption solutions in use have been validated under the Cryptographic Module Validation Program to confirm compliance with FIPS 140-2. The Contractor shall provide a written copy of the validation documentation to the COR upon request.

e. Use the Key Management system on the HHS personal identification verification (PIV) card or establish and use a key recovery mechanism to ensure the ability for authorized personnel to encrypt/decrypt information and recover encryption keys. Encryption keys shall be provided to the COR upon request and at the conclusion of the contract.

Contractor Non-Disclosure Agreement (NDA). Each Contractor (and/or any subcontractor) employee having access to non-public government information under this contract shall complete the HHS/CDC non-disclosure agreement. A copy of each signed and witnessed NDA shall be submitted to the Contracting Officer (CO) and/or CO Representative (COR) prior to performing any work under this acquisition.

Rules of Behavior

1) The Contractor (and/or any subcontractor) shall ensure that all employees performing on the contract comply with the HHS Information Technology General Rules of Behavior.

2) All Contractor employees performing on the contract must read and adhere to the Rules of Behavior before accessing Department data or other information, systems, and/or networks that store/process government information, initially at the beginning of the contract and at least annually thereafter, which may be done as part of annual CDC Security Awareness Training. If the training is provided by the contractor, the signed ROB must be provided as a separate deliverable to the CO and/or COR per defined timelines above.

Incident Response. A privacy breach is a type of incident and is defined by Federal Information Security Modernization Act (FISMA) as the loss of control, compromise, unauthorized disclosure, unauthorized acquisition, or any similar occurrence where (1) a person other than an authorized user accesses or potentially accesses personally identifiable information (PII) or (2) an authorized user accesses or potentially accesses personally identifiable information for an other than authorized purpose. The HHS Policy for IT Security and Privacy Incident Reporting and Response further defines a breach as “a suspected or confirmed incident involving PII”.

In the event of a suspected or confirmed incident or breach, the Contractor (and/or any subcontractor) shall:

1) Protect all sensitive information, including any PII created, stored, or transmitted in the performance of this contract so as to avoid a secondary sensitive information incident with FIPS 140-2 validated encryption.

2) NOT notify affected individuals unless so instructed by the Contracting Officer or designated representative. If so instructed by the Contracting Officer or representative, the Contractor shall send CDC approved notifications to affected individuals.

3) Report all suspected and confirmed information security and privacy incidents and breaches to the CDC Incident Response Team (IRT) (CSIRT@cdc.gov, 866-655-2245), COR, CO, CDC SOP

(or his or her designee), and other stakeholders, including incidents involving PII, in any medium or form, including paper, oral, or electronic, as soon as possible and without unreasonable delay, no later than one (1) hour, and consistent with the applicable CDC and HHS policy and procedures, NIST standards and guidelines, as well as US-CERT notification guidelines. The types of information required in an incident report must include at a minimum: company and point of contact information, contract information, impact classifications/threat vector, and the type of information compromised. In addition, the Contractor shall:

a. cooperate and exchange any information, as determined by the Agency, necessary to effectively manage or mitigate a suspected or confirmed breach;

b. not include any sensitive information in the subject or body of any reporting e-mail; and

c. encrypt sensitive information in attachments to email, media, etc.

4) Comply with OMB M-17-12, Preparing for and Responding to a Breach of Personally Identifiable Information and HHS/CDC incident response policies when handling PII breaches.

5) Provide full access and cooperate on all activities as determined by the Government to ensure an effective incident response, including providing all requested images, log files, and event information to facilitate rapid resolution of sensitive information incidents. This may involve disconnecting the system processing, storing, or transmitting the sensitive information from the Internet or other networks or applying additional security controls. This may also involve physical access to contractor facilities during a breach/incident investigation.

Sanitization of Government Files and Information. As part of contract closeout and at expiration of the contract, the Contractor (and/or any subcontractor) shall provide documentation or attestation to the CO and/or COR to certify that, at the government’s direction, all electronic and paper records are appropriately disposed of and all devices and media are sanitized in accordance with NIST SP 800-88, Guidelines for Media Sanitization.

Contractor Responsibilities Upon Physical Completion of the Contract. The contractor (and/or any subcontractors) shall return all government information and IT resources (i.e., government information in non-government-owned systems, media, and backup systems) acquired during the term of this contract to the CO and/or COR. Additionally, the Contractor shall provide a certification that all government information has been properly sanitized and purged from Contractor-owned systems, including backup systems and media used during contract performance, in accordance with HHS and/or CDC policies.

Records Management and Retention. The Contractor (and/or any subcontractor) shall maintain all information in accordance with Executive Order 13556 -- Controlled Unclassified Information, National Archives and Records Administration (NARA) records retention policies and schedules and HHS policies and shall not dispose of any records unless authorized by HHS.

In the event that a contractor (and/or any subcontractor) accidentally disposes of or destroys a record without proper authorization, it shall be documented and reported as an incident in accordance with HHS policies.