The primary objective of the Informatics Core is to contribute to the science and operation of the Program Project by providing the informatics infrastructure and specialized technical expertise required to support the complex data integration and analysis needs of the grant. The scientific goals of the Projects are highly integrated and will require the analysis of shared data in an iterative fashion throughout the five years. The Core is split into two teams, each with its own faculty director. The University of Minnesota team (MN Team) is led by Dr. Sarah Cooley, Director of the Masonic Cancer Center Medical Informatics Shared Resources. The MN team is responsible for the development and maintenance of database applications to collect, integrate and report research data generated by the projects for subsequent analysis. In addition they will support and customize the clinical trials management application to meet the research and regulatory data requirements for the complex (phase I, IND, multi-center) trials in Projects 2 and 3. The sharing of research samples will be coordinated through this Core with a customized sample inventory management tool. Lastly, this team will develop and support the SOPs for data quality, data integrity, and data sharing, in compliance with HIPAA and caBIG principles. This team has collaborated in the development of the scientific plan by developing data collection and management plans specific to each aim, and will remain actively involved with each Project and Core throughout the life of this grant to monitor data quality and prepare datasets for analysis. The second team, led by Dr. Steven GE Marsh from the Anthony Nolan Trust, is responsible for the unique and specialized tools required for the storage, sharing and analysis of immunogenetic KIR data. The IPD-KIR database was established during the first cycle of this POI, and has proved a valuable resource for data analysis. They will confine to produce software tools to calculate KIR gene frequencies, allele frequencies and to estimate haplotypes and their frequencies at allelic level, define new alleles discovered by the Projects and Core D, and provide data crucial for the development of the high-resolution typing strategy to be employed in Project 1 (Parham) and Core D. Additionally they will provide sequence alignment tools for the analysis and visualization of the intergenic regions between KIR genes (Project 2). To support the clinical trials, they will develop a simple tool to predict the KIR haplotypes in any given individual, and indicate their content in terms of the centromeric and telomeric portions of the haplotype. The scientific expertise provided by this team will be invaluable to analyze and interpret immunogenetic data.
The Program Project grant, which includes three clinical trials and multiple laboratory-based research studies, will generate significant amounts of complex data from mulfiple sites, all of which must be integrated for definifive analysis. This Core contains Faculty and staff at the University of Minnesota and from the Anthony Nolan Trust to develop and support the requisite informatics tools to support the clinical trials and basic research aims.
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|Cichocki, Frank; Schlums, Heinrich; Li, Hongchuan et al. (2014) Transcriptional regulation of Munc13-4 expression in cytotoxic lymphocytes is disrupted by an intronic mutation associated with a primary immunodeficiency. J Exp Med 211:1079-91|
|Cooley, Sarah; Weisdorf, Daniel J; Guethlein, Lisbeth A et al. (2014) Donor killer cell Ig-like receptor B haplotypes, recipient HLA-C1, and HLA-C mismatch enhance the clinical benefit of unrelated transplantation for acute myelogenous leukemia. J Immunol 192:4592-600|
|Bachanova, Veronika; Miller, Jeffrey S (2014) NK cells in therapy of cancer. Crit Rev Oncog 19:133-41|
|Foley, Bree; Felices, Martin; Cichocki, Frank et al. (2014) The biology of NK cells and their receptors affects clinical outcomes after hematopoietic cell transplantation (HCT). Immunol Rev 258:45-63|
|Miller, Jeffrey S; Rooney, Cliona M; Curtsinger, Julie et al. (2014) Expansion and homing of adoptively transferred human natural killer cells in immunodeficient mice varies with product preparation and in vivo cytokine administration: implications for clinical therapy. Biol Blood Marrow Transplant 20:1252-7|
|Felices, Martin; Lenvik, Todd R; Ankarlo, Dave E M et al. (2014) Functional NK cell repertoires are maintained through IL-2R? and Fas ligand. J Immunol 192:3889-97|
|Gleason, Michelle K; Ross, Julie A; Warlick, Erica D et al. (2014) CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. Blood 123:3016-26|
|Sarkar, Chandrima; Cooley, Sarah; Srivastava, Jaideep (2014) Robust Feature Selection Technique using Rank Aggregation. Appl Artif Intell 28:243-257|
|Bachanova, Veronika; Cooley, Sarah; Defor, Todd E et al. (2014) Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood 123:3855-63|
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