Computational Reconstruction of NF kappa B Pathway Interaction Mechanisms during Prostate Cancer
PLOS COMPUTATIONAL BIOLOGY
Authors: Boernigen, Daniela; Tyekucheva, Svitlana; Wang, Xiaodong; Rider, Jennifer R.; Lee, Gwo-Shu; Mucci, Lorelei A.; Sweeney, Christopher; Huttenhower, Curtis
Abstract
Molecular research in cancer is one of the largest areas of bioinformatic investigation, but it remains a challenge to understand biomolecular mechanisms in cancer-related pathways from high-throughput genomic data. This includes the Nuclear-factor-kappa-B (NF kappa B) pathway, which is central to the inflammatory response and cell proliferation in prostate cancer development and progression. Despite close scrutiny and a deep understanding of many of its members' biomolecular activities, the current list of pathway members and a systems-level understanding of their interactions remains incomplete. Here, we provide the first steps toward computational reconstruction of interaction mechanisms of the NF kappa B pathway in prostate cancer. We identified novel roles for ATF3, CXCL2, DUSP5, JUNB, NEDD9, SELE, TRIB1, and ZFP36 in this pathway, in addition to new mechanistic interactions between these genes and 10 known NF kappa B pathway members. A newly predicted interaction between NEDD9 and ZFP36 in particular was validated by co-immunoprecipitation, as was NEDD9' s potential biological role in prostate cancer cell growth regulation. We combined 651 gene expression datasets with 1.4M gene product interactions to predict the inclusion of 40 additional genes in the pathway. Molecular mechanisms of interaction among pathway members were inferred using recent advances in Bayesian data integration to simultaneously provide information specific to biological contexts and individual biomolecular activities, resulting in a total of 112 interactions in the fully reconstructed NF kappa B pathway: 13 (11%) previously known, 29 (26%) supported by existing literature, and 70 (63%) novel. This method is generalizable to other tissue types, cancers, and organisms, and this new information about the NF kappa B pathway will allow us to further understand prostate cancer and to develop more effective prevention and treatment strategies.
A ROBUST GENETIC ALGORITHM FOR FEATURE SELECTION AND PARAMETER OPTIMIZATION IN RADAR-BASED GAIT ANALYSIS
2019 IEEE 8TH INTERNATIONAL WORKSHOP ON COMPUTATIONAL ADVANCES IN MULTI-SENSOR ADAPTIVE PROCESSING (CAMSAP 2019)
Authors: Dawel, Lisa; Seifert, Ann-Kathrin; Muma, Michael; Zoubir, Abdelhak M.
Abstract
Contactless medical gait analysis plays an important role in assessing health conditions for ambient assisted living. Prior work on radar-based gait analysis has mainly focused on classification of different gaits or detecting asymmetry. We demonstrate that it is possible to estimate medically relevant gait characteristics based on features from the radar back-scatterings. Given a set of radar features, we predict the maximal knee angle during walking for the left and right leg. We present a new robust genetic algorithm (GA) based on a nonlinear regression method that simultaneously performs feature sele ction, parameter optimization for the support vector machine and outlier rejection by encoding these aspects into the chromosome design. Using genetic operations, the proposed algorithm significantly outperforms competing methods on a real-world data set recorded with a 24 GHz continuous-wave radar.