Francisco Arsuaga, Ph.D.

Profile Introduction

I develop mathematical and computational methods to address questions that arise in the study of the 3D structure of chromosomes. The three dimensional (3D) structure of the genome plays a key role in the dynamics of the living cell tightly regulating essential biological processes such as transcription, replication and repair. In humans, disruption of the 3D structure of the genome, in the form of large-scale rearrangements and copy number changes, is the signature of DNA-damaging agents and has been associated with a wide range of diseases, including cancer. In parasitic organisms, the 3D structure of the genome is a frequent drug target. Descriptions of the 3D structure genomes however have remained elusive even for the simplest organism.

In our most recent research we are developing new mathematical methods to characterize the packing of DNA in: dsDNA bacteriophages, mitochondrial DNA in trypanosomes (kDNA) and yeast. 

Grad Group Affiliations

• Biochemistry, Molecular, Cellular and Developmental Biology
• Biostatistics, Statistics
• Mathematics 

Honors and Awards

• 2018 Plenary speaker: Abel Symposium, Geiranger, Norway.
• 2018 Plenary speaker: Encuentros en Algebra Computacional y Aplicaciones (EACA), Zaragoza, Spain.
• 2013-2014 Long Term Visitor of the Institute of Mathematics and Its Applications (IMA), Minneapolis, MN
• 2012 Plenary speaker: “Conference in Computational Physics”, Kobe, Japan
• 2011 Research selected by NSF for the NSF highlights
• 2007 Lont Term Visitor of the Institute of Mathematics and Its Applications (IMA), Minneapolis, MN
• 1997-2000 Fellow of the Program in Mathematics and Molecular Biology (PMMB)

Professional Societies

• American Association for the Advancement of Science (AAAS)
• American Society for Virology (ASV)
• American Mathematical Society (AMS)
• Society for Industrial and Applied Mathematics (SIAM)

Selected Works

Topological analysis of DNA packing in bacteriophages 

9. Arsuaga J. Vazquez M., Hiltner L, Calderer C. Liquid crystal model of viral DNA encapsidation (Submitted). 

8. Arsuaga J., Roca J. and Sumners D. W. Topology of viral DNA. (Book chapter) in "Emerging Topics in Physical Virology" Imperial College Press. (2010) Ed. P. G. Stockley and R. Twarock.

7. Arsuaga J, Diao Y and Vazquez M Mathematical methods in DNA topology: Applications to chromosome organization and site-specific recombination. IMA volumes in Mathematics and Its Applications. Volume 150: Mathematics of DNA Structure, Function, and Interactions (2009) Edited by Craig John Benham, Stephen Harvey, Wilma K. Olson, De Witt L. Sumners, and David Swigon. Springer Science + Business Media, LLC, New York. (Book chapter)

6. Arsuaga J, and Diao Y (2008) DNA knotting in Spooling like conformations in Bacteriophages. Journal Computational and Mathematical Methods in Medicine 9 (3-4) 303-316.

5. Hua X, Nguyen D, Raghavan B, Arsuaga J, Vazquez M. (2007) Random state transitions of knots: a first step towards modeling unknotting by type II topoisomerases. Topology and its Applications.154(7):1381-97.

4. Arsuaga, J., Vazquez, M., McGuirk, P., Sumners D.W. and Roca J. (2005) DNA knots reveal a chiral organization of DNA in phage capsids. Proceedings of the National Academy of Sciences USA. 102(26):9165-9

3. Arsuaga, J., Tan, R., Vazquez, M., Sumners, D. W., and Harvey, S. C. (2002) Investigation of Viral DNA Packaging Using Molecular Mechanics Models. Biophysical Chemistry, 101-102(1): 475-484.

2. Arsuaga J, Vazquez, M., Trigueros, S., Sumners, D. W., and Roca, J. (2002) Knotting probability of DNA molecules confined in restricted volumes: DNA knotting in phage capsids. Proceedings of the National Academy of Sciences USA 2002, 99(8):5373-5377

1. Trigueros, S., Arsuaga, J., Vazquez, M., Sumners, D.W., Roca, J. (2001) Novel display of knotted DNA molecules by two dimensional gel electrophoresis. Nucleic Acids Research, 29 (13): e67.

Genomic Analysis of the bacterial chromosome

2. Postow, L., Hardy, C., Arsuaga, J. and Cozzarelli, N. R. (2004) Topological domain structure of the Escherichia coli chromosome. Genes and Development. 18(14):1766-79.

1. Peter, B., Arsuaga, J., Breier, A., Khodursky, A., Brown, P., and Cozzarelli N. R. (2004) Genomic analysis of supercoiling sensitive genes in Escherichia coli: responses to topoisomerase inhibition. Genome Biology 5 (11) R-87.

Topological analysis of Kinetoplast DNA

9. Ibrahim L., Liu P., Diao Y., Michele K and Arsuaga J. Estimating properties of kDNA by unlinking reactions. (Submitted). 

8. Diao Y., Hinson K., Sun Y. and Arsuaga J. (2015) The effect of volume exclusion on the formation of DNA minicircle networks. J. Phys. A  Math Theor. 48 (43) 435202

7. Diao Y., Rodriguez V., Klingbeil M and Arsuaga J. Orientation of DNA minicircles balances density and topological complexity in kinetoplast DNA. Plos One 10(6): e0130998. 

6. Arsuaga J., Diao Y, Klingbeil M. and Rodriguez V. (2014) Properties of Topological Networks of Flexible Polygonal Chains. Mol. Based. Math. Bio. 2: 98-106.

5. Rodriguez V, Diao Y. and Arsuaga J. (2013) Percolation phenomena in randomized topological networks. J. Phys.: Conf. Ser.  454 012070

4. Arsuaga J, Diao Y and Hinson K (2012) The effect of angle restriction on the topological characteristics of minicircle networks. J. Stat. Phys. 146: 434-445.

3. Arsuaga J, Diao Y and Hinson K, (2012) The growth of minicircle networks on regular lattices, J. of Phys. A: Math. Theor. 45 035004

2. Diao Y, Hinson K, Kaplan R, Vazquez M, and Arsuaga J (2012) The effects of minicircle density on the topological structure of the mitochondrial DNA from trypanosomes. Journal of Mathematical Biology 64(6) 1087-1108 

1. Arsuaga, J., Blackstone, T., Diao,Y., Karadayi, E. , Saito, Y. (2007)  Linking of Uniform Random Polygons in Confined Spaces. J. Phys. A: Math. Gen. 40: 1925-1936

Statistical analysis of the yeast genome

2. Pouokam M, Cruz B, Burgess S, Segal M, Vazquez M, Arsuaga J Quantification of entanglement complexity of the yeast genome reveals a bias towards topological simplicity (Submitted). 

1. Segal M, Xiong H, Capurso D, Vazquez M and Arsuaga J (2014) Reproducibility of three-dimensional chromatin configuration reconstructions. Biostatistics 15(3): 442-56. 

Statistical, topological and combinatorial analysis of large scale organization of the human genome

7. Nicolau M, Erler JT, Theilgaard-Monch K, Arsuaga J. Comparative Chromosomal Folding Analysis (Submitted). 

6. Arsuaga J., Heskia I., Hosten S., and Maskalevich T. (2015) Uncovering Proximity of Chromosome Territories using Classical Algebraic Statistics. Journal of Algebraic Statistics. 6 (2):133-149.  

5. Arsuaga J., Jayasinghe R., Scharein R, Segal M and Vazquez M. (2015) Current analytical methods are insufficient to determine the topological complexity of the human genome. Frontiers in Molecular Biosciences, section Mathematics of Biomolecules 2(48). 

4. Blackstone, T, Scharein, R., Varela, R., Diao, Y., and Arsuaga J. (2011) Modeling Chromosome Intermingling Using Overlapping Uniform Random Polygons. Journal of Mathematical Biology  62(3): 371-89.

3. Vives, S., Bradford, L., Vazquez, M., Brenner, D., Sachs, R. K., Hlatky, L., Cornforth, M. and Arsuaga, J. (2005) SCHIP: Statistics of Chromosome Interphase Positioning based on interchange data. Bioinformatics 21(14):3181-2.

2. Arsuaga, J., Greulich-Bode, K., Vazquez, M., Brukner, M.,Hahnfeldt,P., Brenner, D.J., Sachs, R. and Hlatky, L. (2004) Chromosome positioning through radiogenic aberrations. International Journal of Radiation Biology 80 (7), 507-516.

1. Cornforth, M. N., Greulich-Bode, K. M., Loucas, B. D., Arsuaga, J., Vazquez, M., Daye,J., Sachs, R. K.,Bruckner, M., Molls, M., Hahnfeldt, P., Hlatky, L., Brenner, D. J. (2002) Chromosomes are predominantly located randomly with respect to each other in interphase human cells. The Journal of Cell Biology 159 (2), 237-244.

Combinatorial and statistical analysis of radiation induced chromosome aberrations

3. Levy, D., Vazquez, M., Loucas, B. D., Cornforth, M. N., Sachs, R. K., Arsuaga, J. (2004) Comparing DNA damage-processing pathways by computer analysis of chromosome painting data. Journal of Computational Biology 11(4): 626-641.

2. Vazquez, M., Greulich-Bode, K. M., Arsuaga, J., Cornforth, M. N., Bruckner, M., Sachs,R. K., Hahnfeldt, P., Molls, M., Hlatky, L. (2002) Computer analysis of mFISH  chromosome aberration data uncovers an excess of very complex metaphases. International Journal of Radiation Biology 2002, 78(12): 1103-1115.

1. Sachs, R. K., Arsuaga, J., Vazquez, M., Hahnfeldt, P., and Hlatky, L. (2002) Using graph theory to analyze chromosome aberrations. Radiation Research 158 (5): 556-567.

Topological analysis of breast cancer genomic data

5. Ardanza-Trevijano S., Gonzalez G., Borrman T. Garcia J.L. Arsuaga J. (2016) Toplogical Analysis of Amplicon Structure in Comparative Genomic Hybridization (CGH) Data: An Application to ERBB2/HER2/NEU Amplified Tumors. Lecture Notes in Computer Science. 9667, Springer 2016, ISBN 978-3-319-39440-4 (Peer Reviewed Book Chapter)

4. Arsuaga J., Borrman T., Cavalcante R., Gonzalez G. and Park C (2015) Identification of Copy Number Aberrations in Breast Cancer Subtypes using Persistence Topology. Microarrays 4 (3), 339-369

3. Arsuaga J , Baas N, DeWoskin D, Mizuno H, and Pankov A, Park C (2012) A topological signature derived from expression profiles for the identification of breast cancer subtypes. Applicable Algebra in Engineering, Communication and Computing 23 (1) 3-15. 

2. DeWoskin, D., Climent, J., Cruz-White, I., Vazquez, M., Park, C. and Arsuaga, J. (2010) Applications  of Computational Homology to Prediction of Treatment Response in Breast Cancer Patients. Topology and Its Applications. 157 (1) 157-164

1. Climent, J., Mao, J., Garcia, J. L., Arsuaga, J., Perez-Losada, J. (2007) Characterization of Breast Cancer by Array CGH. Biochemistry and Cell Biology  85(4); 497-508 (Review)

Biologically Motivated Basic Principles of Polymer Physics   

9. Ishihara, K; Pouokam, M; Suzuki, A; Scharein, R; Vazquez, M; Arsuaga, J; Shimokawa,
K (2017) Bounds for minimum step number of knots confined to tubes in the
simple cubic lattice J. of Phys. A : Math. Theor. 50 (21). 

8. Ishihara K, Scharein R, Diao Y, Arsuaga J, Vazquez M, Shimokawa K (2012) Bounds for minimum step number of knots confined to slabs in the simple cubic lattice. J. of Phys. A : Math. Theor. 45 065003 

7. Portillo J, Diao Y,Scharein R, Arsuaga J and Vazquez M (2011) On the mean and the variance of the writhe. J. Phys A: Math Theor. 44 275004.

6. Arsuaga J, Borgo B, Diao Y and Scharein R (2009) The Average Crossing Number of Equilateral Random Polygons in Confined Volumes. J. Phys. A: Math. Theor. 42 465202. 

5. Scharein R, Ishihara K, Arsuaga J, Shimokawa K, Vazquez M (2009) Bounds for minimal step number of knots in the simple cubic lattice. J. Phys A: Math. and Theor 42 475006-457030

4. Varela R, Hinson K, Arsuaga J, Diao Y (2009) A fast ergodic algorithm for generating ensembles of polygons. J. Phys A: Math Theor.  42 095204 .

3. Arsuaga J, Blackstone T, Diao Y, Karadayi E, Saito Y (2007)  Knotting of Uniform Random Polygons in Confined Spaces. J. Phys. A: Math Gen. 40: 11697-11711

2. Blackstone T, McGuirk P, Laing C, Vazquez M, Roca J, and Arsuaga J. (2007) The role of writhing in DNA condensation. Proceedings of International Workshop on Knot Theory for Scientific Objects. OCAMI Studies Volume 1 (2) Osaka Municipal. Universities Press; 239-250 Osaka, Japan

1. Ardanza-Trevijano S. Arsuaga J, Crespo JA, Extremiana J I, Hernandez LJ, Rivas MT, Roca J, Vazquez M (2007) La topologia como herramienta en otros campos. La Gaceta de la Real Sociedad Matematica Espanola 10 (3); 911-932. (Review)