Bionformatics_-_SOW.docx

Statement of Work Purpose The National Institute of Nursing Research (NINR), Division of Intramural Research (DIR) investigators require bioinformatics expertise to complete genomic analyses in on-going and future projects. Specifically, expertise related to code-based processing and analyses of high throughput sequencing data is required. In addition, oversight of fellows in learning statistical analyses and in undertaking complex analyses of genomic data is needed.

Scope This bioinformatics analysis will be used to complete a number of projects with intramural NINR investigators. Due to the extreme complexity of these analyses, the requirement of weekly meetings on the NIH campus and iterative dialogue with NINR scientists is essential to interpret the data and to make inferences related to biological phenotype data. This genome-wide analysis requires expertise in big data analysis and bioinformatic interpretation. In addition, oversight of NINR post-doctoral fellows in data analyses is essential for data integrity and also to meet training goals. This requires evidence of teaching and mentoring; therefore, the ideal applicant will have experience mentoring or providing instructions on how to perform genomic analyses courses at the post-doctoral level on over the past 3 years. Lastly, evidence of contribution to the publication of at least 2 manuscripts in peer reviewed journals is required specially in the area of obesity.

Projects include the following:

0. SNPs and array analysis

0. RNA-seq projects

0. Whole genome re-sequencing projects

0. Machine learning projects

0. Natural imaging projects

Tasks Task 1-Direct Research Support Through in Person Meetings and Email

0. Analyze next generation sequence data, including the following required steps: quality checking and mapping to a reference genome. Data analysis for three common applications of next generation sequencing: variant detection, RNA-seq, and ChIP-seq are needed. Presentation and interpretation of the data is then needed. Use bioinformatics and statistical approaches to assess how bio-behavior may affect epi-genetic features (DNA methylation, histone modifications, chromatin states, etc) which may further lead to gene expression changes or diffident clinical outcomes.

0. Analyze microarray data including the following required steps: R, Partek and Plink will be used. Interrogating probes are imported, and corrections for background signal are applied using the robust multi-array average (RMA) method, with additional corrections applied for the GC-content of probes. The probe-sets are standardized using quantile normalization, and expression levels of each probe underwent log-2 transformation to yield distributions of data that more closely approximated normality. Gene-lists will be used to generate pathway analyses using ingenuity pathway analysis.

0. Conduct comparative genomics and population genetic study for taste receptor genes. Analysis include but not limited to computing Ka, Ks and Ka/Ks, drawing phylogenetic tree using MEGA, gene duplication mode and synteny analysis using MCScanX, gene regulation analysis using DNA motif detection tools (e.g. FIMO), evolution of epigenetic features (e.g. DNA methylation), functional outcome of SNPs in the human populations (i.e. continuing our previous analyses).

0. Apply deep neural network (DNN) approach to generate advanced precision medicine models for obesity risks (or other clinical outcomes). Analysis will include several predictors such as bio-behaviors, lab results, genetic information (gene expression, SNPs, etc) and epi-genetic information.

0. Apply convolutional neural network (CNN) approach to classify medical images (e.g. healthy vs. disease, disease subtypes, prognoses).

0. Give consultation on proteomic data including the following required steps: R will be used to examine distribution of data, means, standard deviations and other group factors. Cofactors will be examined using group variation and regression methods.

0. Apply advanced bioinformatics and statistical models to identify intrinsic and sophisticated relationships between miRNA and gene expression.

0. Figures will be developed to present the data for publication. Interpretation of data with NINR investigators will be necessary.

0. Provide study design documentation prior to the internal analysis requested by a NINR/DIR Investigator

0. Provide figures, diagrams and power analyses and summary of analysis based on approved study design

Task 2 - Project Management and Reporting Support (Task Order Management Plan)

14. Provide verbal and written status updates as requested by the project officer.

Task 3- Training and oversight of fellows in data analyses

14. Meet with fellows to discuss approach of laboratory analyses and provide didactic teaching when required on a weekly basis and as needed.

14. Provide theoretical and technical advisement throughout the study to NINR investigators weekly and as needed. This will range from advisement on study design to the writing of findings to be included in publications.

14. Oversee analysis methods and result interpretation with fellows and NINR investigators through on-site meetings, email and other correspondence.

Government Responsibilities The Government will:

· Provide next generation sequence data

· Provide microarray data

· Provide protein data

· Provide imaging data

· Organize weekly meeting

· Follow instruction for data collection

· Inform any critical changes in data collection

Responsibilities of the Contractor

· Weekly meetings to provide updates, discussion and progress projects

· Availability during normal business hours to address critical issues in data analyses and interpretation as needed

· Supply all necessary computer infrastructure including statistical programs to analyze data

· Provide oversight to NINR fellows to meet training needs in regard to data analyses in genomics. Didactic teaching analyses methods when required. This will include on-site overseeing of data analyses, as well as more formal teaching as needed.

Duty Station The place of performance is in Bethesda, MD 20814. This work may also be performed remotely at the discretion of NINR investigators.

Period of Performance Estimated : Base (2018), plus two optional years.

Contract Type This is a firm fixed-price type order.