1. Literature Review: Optical Mapping As A Method of Whole Genome Analysis, 2. Literature Review: Optimizing Patient Flow in the Healthcare System, 3. Application: Automated Building Block Definitions Using Graphs and Graph Tree Searching, Austin Ramme

Austin Ramme’s Project Proposals

Austin Ramme’s Project Proposals

Literature Review: Optical Mapping As A Method of Whole Genome Analysis

Optical mapping offers a means to perform whole genome analysis using ordered restriction maps that are generated using microfluidic deposition of fluorescently labeled DNA molecules onto electrically charged surfaces that are later exposed to restriction enzymes. The DNA is electrically fixed to the charged surface and thus the order of the restriction fragments is maintained. The analysis of the data obtained from imaging this data has proven to be very challenging and many formulations have proven to be NP-hard.

Various problems including incomplete digestions and small DNA fragments add a great deal of complexity to the analysis of this data set. However, several groups have developed formulations that allowed for polynomial time solving. Relatively recently a new algorithm for handling this data using graph structure and error reduction techniques was introduced and has proven to be quite powerful. This new algorithm has allowed for the optical mapping of very large genomes (rice and human), which could allow for the identification of new genetic variations correlated with a wide variety of diseases.

References:

Valouev A, Schwartz DC, Zhou S, Waterman, MS. An algorithm for assembly of ordered restriction maps from single DNA molecules. PNAS 2006; 103(43):15770-15775.

Valouev A, Zhang Y, Schwartz DC, Waterman, MS. Refinement of optical map assemblies. Bioinformatics 2006; 22(10):1217-1224.

Literature Review: Optimizing Patient Flow in the Healthcare System

Rising costs and limited resources in the healthcare industry have led to the need for optimization of resource organization and allocation. Various models have been developed, one of which is Discrete Event Simulation (DES). DES allows for the evaluation of efficiency of existing processes. It also allows for evaluation of potential changes to the status quo including modifications to patient flow, staffing levels, and physician capacity. It also allows for an investigation of relationships between complex variables like rates of patient arrival and service delivery. DES uses discrete criteria and graphing to find optimal work flows. Applications to almost every department within a hospital have been proposed using different criteria and fiscal goals. Overall, DES offers a means to better understand the structure of a healthcare system and changes made to it.

References:

Jacobson SH, Hall SN, Swisher. Discrete-Event Simulation of Health Care Systems. In: Hall R, ed. Patient Flow: Reducing Delay in Healthcare Delivery. 2006: 211-252.

Yucesan E, Jacobson SH. Computational issues for accessibility in discrete event simulation. ACM Transaction on Modeling and Computer Simulation. 1996; 6(1): 53-75.

Application: Automated Building Block Definitions Using Graphs and Graph Tree Searching

In the design of medical devices, stress analysis is often employed to ensure that all components of a device operate below the threshold for fatigue and failure. The finite element method has been used to analyze biological tissues such as bone, ligaments, and articular cartilage in a variety of applications including fracture risk and prosthetic design. IA-FEMesh is an open-source software package under development to facilitate engineering analysis and surgical planning using the finite element method. The first version of the software was released in the summer of 2008 and has had more than 200 downloads. The current software allows the user to load a three dimensional surface, define building blocks, generate a hexahedral mesh based on the building blocks, and assign material properties to the element sets. The final data set can then be used for finite element analysis in software like ABAQUS.

The current software includes tools that allow for manual placement of building blocks that are essential for mesh generation on a surface. Automation of this process often results in an array of overlapping building blocks, which is unacceptable. This project would center on developing a tree style solution to untangling the building blocks based on the discrete number of overlap possibilities. It would also involve developing a tree searching algorithm to optimize the untangling process. Developing this organization style could improve on the efficiency of the current technique.

Reference:

Grosland NM, Shivanna KH, Magnotta VA, Kallemeyn NA, DeVries NA, Tadepalli SC, Lisle C. IA-FEMesh: An open-source, interactive, multiblock approach to anatomic finite element model development. Computer Methods and Programs in Biomedicine 2009; [In press].