MacLeod, James

Owned by UKY CCS RCD
Jun 09, 2024
4 min read

Introduction


The MacLeod laboratory studies biological and biomedical aspects of the musculoskeletal system, with an emphasis on growth and maturation of articular cartilage, development and progression of osteoarthritis, the repair of articular lesions, and effects of anti-inflammatory medications. Experiments are conducted primarily on a cellular and molecular level. Additional projects focus on cervical stenosis myeolpathy and analyses of the equine transcriptome.

The transcriptome studies include annotation of equine protein-coding gene structures and characterization of the articular chondrocyte transcriptome relative to chondrocytes in other cartilaginous tissues. The research includes projects with Dr. Jinze Liu in the Department of Computer Science that have utilized HPC resources, involving efforts to characterize the complexity of mRNA splicing patterns and develop computational methods for the analysis of high throughput RNA sequencing data.

The Kalbfleisch lab works to utilize high throughput genetic data to better understand the impact of genetic structure and variation on human and animal health. To this end, they develop informatics infrastructure to support the storage, organization, and use of large genomic datasets. He currently works with collaborators at the USDA to identify variation in their founder bull population at the Meat Animal Research Center in Clay Center, Nebraska for use in genome wide association studies. Dr. Kalbfleisch and Dr. MacLeod have worked together to ask similar questions of equine genomics data. Dr. Kalbfleisch, a University of Louisville faculty member works often with the High Performance Computing resources at the University of Louisville, and with HPC Research Computing team member Mr. Harrison Simrall on projects that involve the mapping and analysis of high throughput sequence data sets. His projects are typically memory, cpu, and I/O intensive.

In their current collaboration, Drs. Kalbfleisch and MacLeod are working to generate an improved equine reference genome sequence.

Project- Creation of a new Reference Genome for the Domestic Horse

This project entails identification of overlaps, or partial overlaps of genomic sequence reads (strings of DNA characters between 100 and 800 characters in length) to create longer contiguous sequences of genomic DNA representative of the genome sequence for this horse. This process has been benchmarked with the software components we intend to use, and the DLX is a very good match in terms of local storage and available RAM. Dr. Kalbfleisch and Mr. Simrall will be the ones performing the computational work, and Dr. MacLeod will assist in the evaluation of the new reference sequence that is produced.

Collaborators:

Prof. Ted kalbfleisch UofL
Harrison Simrall UofL
Michael Scotty DePriest UofL/UKY split appointment

Collaborators:

Prof. James MacLeod (UK sponsor) (co-project lead)
Prof. Jinze Liu - (UK CS) - involving efforts to characterize the complexity of mRNA splicing patterns and develop computational methods for the analysis of high throughput RNA sequencing data.
Asst. Prof. Ted Kalbfleisch (UofL) (co-project lead)
Mr. Harrison Simrall (UofL IT, Research Computing) -will be the ones responsible for loading the software, and the data, as well as the execution of the software to which will perform the assembly.

Computational Methods:

The Celera Assembler uses an overlap method for aligning long reads. The MaSuRCA assembler is a “… new hybrid approach that has the computational efficiency of de Bruijn graph methods and the flexibility of overlap-based assembly strategies, and which allows variable read lengths while tolerating a significant level of sequencing error.”

Software:

Celera Assembler (http://sourceforge.net/apps/mediawiki/wgsassembler/
index.php?title=Main_Page)
MaSurCA (http://bioinformatics.oxfordjournals.org/content/29/21/2669.abstract.html?etoc) They will be downloaded as source, and compiled to run on the DLX.

Online Bioinformatics Course

UKY Alejandro Esteller-Vico, is hosting an Online Bioinformatics Course at UofL. Professor Ted Kalbfleisch will be instructing the online Bioinformatics course for UKY faculty, postdocs, staff, and students.

Participants:

Kalbfleisch, Ted - Instructor
Esteller-Vico, Alejandro - Faculty, UKY Veterinary Science
Ball, Barry A - Faculty, Veterinary Science
Loux, Savahn C - Postdoc, Veterinary Science
Scoggin, Kirsten E - Staff, Veterinary Science
Thampi, Parrathy - Student, Veterinary Science
Mok, Chanhee - Student, Veterinary Science
Adam, Emma N - Student, Veterinary Science
Fleming, Blaire O - Student, Veterinary Science
Goedde, Lauren D - Student, UK Veterinary Science
Fedorka, Carleigh E - Student, Veterinary Science
Dini, Pouya - Visiting Scholar, Veterinary Science
Linhares Boakari, Yatta - Student, Veterinary Science
Fernandes, Claudia B - Visiting Scholar, Veterinary Science
Wynn, Michelle A A - Student, Veterinary Science
MacLeod, James N - Faculty, UKY Veterinary Science

Publications:


2013

  1. Huang Y, Hu Y, Jones CD, MacLeod JN, Chiang DY Liu Y, Prins JF, Liu J. A Robust Method for Transcript Quantification with RNA-seq Data. Journal of Computational Biology, 20:167-187, 2013.
  2. Coleman SJ, Zeng Z, Hestand MS, Liu, J., MacLeod JN. 2013. Analysis of unannotated equine transcripts identified by mRNA sequencing. PLoS One, 8: e70125. doi: 10.1371.


2012

  1. Cosden RS, Bickett MM, Lattermann C, MacLeod JN. Structural and functional analysis of intra-articular interzone tissue in axolotl salamanders. Osteoarthritis and Cartilage, 20:1347-1356, 2012.


2011

  1. Cosden RS, Lattermann C, Romine S, Gao J, Voss SR, MacLeod JN. Intrinsic repair of full-thickness articular cartilage defects in the axolotl salamander. Osteoarthritis and Cartilage, 19:200-205, 2011.
  2. Kikuchi M, Nakano Y, Nambo Y, Haneda S, Matsui M, Miyake Y, MacLeod JN, Nagaoka K, Imakawa K. Production of Calcium Maintenance Factor Stanniocalcin-1 (STC1) by the Equine Endometrium During the Early Pregnant Period. Journal of Reproduction and Development, 57:203-211, 2011.
  3. Vanderman KS, Tremblay M, Zhu W, Shimojo M, Mienaltowski MJ, Coleman SJ, MacLeod JN. Brother of CDO (BOC) Expression in Articular Cartilage. Osteoarthritis and Cartilage, 19:435-438, 2011.
  4. Go YY, Bailey E, Cook DG, Coleman SJ, MacLeod JN, Chen KC, Timoney PJ, Balasuriya UB. Genome-Wide Association Study Among Four Horse Breeds Identifies a Common Haplotype Associated with the In Vitro CD3+ T Cell Susceptibility/Resistance to Equine Arteritis Virus Infection. Journal of Virology, 85:13174-13184. 2011.


2010

  1. Mienaltowski MJ, Huang L, Bathke A, Stromberg AJ, MacLeod JN. Transcriptional comparisons between articular repair tissue, neonatal cartilage, cultured chondrocytes, and mesenchymal stromal cells. Briefings in Functional Genomics & Proteomics, 9:238-250, 2010.
  2. Wang K, Singh D, Zeng Z, Coleman SJ, Huang Y, Savich GL, Xiaping H, Mieczkowski P, Grimm SA, Perou CM, MacLeod JN, Chiang DY, Prins JF, Liu J. MapSplice: accurate mapping of RNA-seq reads for splice junction discovery. Nucleic Acids Research, 38(18):e178, 2010.
  3. Coleman SJ, Zeng Z, Wang K, Luo S, Khrebtukova I, Mienaltowski MJ, Schroth GP, Liu, J., MacLeod JN. Structural annotation of equine protein-coding genes determined by mRNA sequencing. Animal Genetics, 41 (Suppl. 2):121–130, 2010.

Grants

MacLeod, James D14EQ-409 Unique patterns of gene expression in articular chondrocytes: important insight for joint surface lesion repair and cell-based therapies $100,000 Morris Animal Foundation 12/1/2013 11/30/2015

Center for Computational Sciences