Abstract
Gene clusters are sets of genes in a genome with associated functionality. Often, they exhibit close proximity to each other on the chromosome which can be beneficial for their common regulation. A popular strategy for finding gene clusters is to exploit the close proximity by identifying sets of genes that are consistently close to each other on their respective chromosomal sequences across several related species.
Yet, even more than gene proximity on linear DNA sequences, the spatial conformation of chromosomes may provide a pivotal indicator for common regulation and/or associated function of sets of genes.
We present the first gene cluster model capable of handling spatial data. Our model extends a popular computational model for gene cluster prediction, called \(\delta \) -teams, from sequences to general graphs. In doing so, \(\delta \)-teams are single-linkage clusters of a set of shared vertices between two or more undirected weighted graphs such that the largest link in the cluster does not exceed a given threshold \(\delta \) in any input graph.
We apply our model to human and mouse data to find spatial gene clusters, i.e., gene sets with functional associations that exhibit close neighborhood in the spatial conformation of the chromosome across species.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Dolinski, K., Dwight, S.S., Eppig, J.T., Harris, M.A., Hill, D.P., Issel-Tarver, L., Kasarskis, A., Lewis, S., Matese, J.C., Richardson, J.E., Ringwald, M., Rubin, G.M., Sherlock, G.: Gene ontology: tool for the unification of biology. Nat. Genet. 25(1), 25–29 (2000)
Beal, M., Bergeron, A., Corteel, S., Raffinot, M.: An algorithmic view of gene teams. Theoret. Comput. Sci. 320(2–3), 395–418 (2004)
Belton, J.M., McCord, R.P., Gibcus, J.H., Naumova, N., Zhan, Y., Dekker, J.: Hi-C: a comprehensive technique to capture the conformation of genomes. Methods 58(3), 268–276 (2012)
Burton, J.N., Adey, A., Patwardhan, R.P., Qiu, R., Kitzman, J.O., Shendure, J.: Chromosome-scale scaffolding of de novo genome assemblies based on chromatin interactions. Nat. Biotechnol. 31(12), 1119–1125 (2013)
Cormen, T.H., Leiserson, C.E., Rivest, R.L.: Introduction to Algorithms. MIT Press, Cambridge (1990)
Díaz-Díaz, N., Aguilar-Ruiz, J.S.: Go-based functional dissimilarity of gene sets. BMC Bioinform. 12(1), 360 (2011)
Didier, G., Schmidt, T., Stoye, J., Tsur, D.: Character sets of strings. J. Discret. Algorithms 5(2), 330–340 (2006)
Dixon, J.R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J.S., Ren, B.: Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485(7398), 376–380 (2012)
He, X., Goldwasser, M.H.: Identifying conserved gene clusters in the presence of homology families. J. Comput. Biol. 12(6), 638–656 (2005)
Jacob, F., Perrin, D., Sanchez, C., Monod, J.: Operon: a group of genes with the expression coordinated by an operator. C. R. Hebd. Seances Acad. Sci. 250, 1727–1729 (1960)
Jahn, K.: Efficient computation of approximate gene clusters based on reference occurrences. J. Comput. Biol. 18(9), 1255–1274 (2011)
Larroux, C., Fahey, B., Degnan, S.M., Adamski, M., Rokhsar, D.S., Degnan, B.M.: The NK homeobox gene cluster predates the origin of Hox genes. Curr. Biol. 17(8), 706–710 (2007)
Ryba, T., Hiratani, I., Lu, J., Itoh, M., Kulik, M., Zhang, J., Schulz, T.C., Robins, A.J., Dalton, S., Gilbert, D.M.: Evolutionarily conserved replication timing profiles predict long-range chromatin interactions and distinguish closely related cell types. Genome Res. 20(6), 761–770 (2010)
Schmidt, T., Stoye, J.: Gecko and GhostFam: rigorous and efficient gene cluster detection in prokaryotic genomes. Methods Mol. Biol. 396, 165–182 (2007). (Chapter 12)
Selvaraj, S., Dixon, J.R., Bansal, V., Ren, B.: Whole-genome haplotype reconstruction using proximity-ligation and shotgun sequencing. Nat. Biotechnol. 31(12), 1111–1118 (2013)
Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., Hoichman, M., Parrinello, H., Tanay, A., Cavalli, G.: Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148(3), 458–472 (2012)
Thévenin, A., Ein-Dor, L., Ozery-Flato, M., Shamir, R.: Functional gene groups are concentrated within chromosomes, among chromosomes and in the nuclear space of the human genome. Nucleic Acids Res. 42(15), 9854–9861 (2014)
Uno, T., Yagiura, M.: Fast algorithms to enumerate all common intervals of two permutations. Algorithmica 26(2), 290–309 (2000)
Wang, B.F., Kuo, C.C., Liu, S.J., Lin, C.H.: A new efficient algorithm for the gene-team problem on general sequences. IEEE/ACM Trans. Comput. Biol. Bioinform. 9(2), 330–344 (2012)
Wang, B.F., Lin, C.H.: Improved algorithms for finding gene teams and constructing gene team trees. IEEE/ACM Trans. Comput. Biol. Bioinform. 8(5), 1258–1272 (2010)
Wang, B.F., Lin, C.H., Yang, I.T.: Constructing a gene team tree in almost O(n lg n) time. IEEE/ACM Trans. Comput. Biol. Bioinform. 11(1), 142–153 (2014)
Winter, S., Jahn, K., Wehner, S., Kuchenbecker, L., Marz, M., Stoye, J., Böcker, S.: Finding approximate gene clusters with Gecko 3. Nucleic Acids Res. 44(20), 9600–9610 (2016)
Yates, A., Akanni, W., Amode, M.R., Barrell, D., Billis, K., Carvalho-Silva, D., Cummins, C., Clapham, P., Fitzgerald, S., Gil, L., Girn, C.G., Gordon, L., Hourlier, T., Hunt, S.E., Janacek, S.H., Johnson, N., Juettemann, T., Keenan, S., Lavidas, I., Martin, F.J., Maurel, T., McLaren, W., Murphy, D.N., Nag, R., Nuhn, M., Parker, A., Patricio, M., Pignatelli, M., Rahtz, M., Riat, H.S., Sheppard, D., Taylor, K., Thormann, A., Vullo, A., Wilder, S.P., Zadissa, A., Birney, E., Harrow, J., Muffato, M., Perry, E., Ruffier, M., Spudich, G., Trevanion, S.J., Cunningham, F., Aken, B.L., Zerbino, D.R., Flicek, P.: Ensembl 2016. Nucleic Acids Res. 44(D1), D710 (2016)
Zhang, M., Leong, H.W.: Gene team tree - a hierarchical representation of gene teams for all gap lengths. J. Comput. Biol. 16(10), 1383–1398 (2009)
Acknowledgements
We are very grateful to Krister Swenson for kindly providing the Hi-C data used in this study and for his many valuable suggestions. We wish to thank Pedro Feijão for many fruitful discussions in the beginning of this project. This work was partially supported by DFG GRK 1906/1.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this paper
Cite this paper
Schulz, T., Stoye, J., Doerr, D. (2017). Finding Teams in Graphs and Its Application to Spatial Gene Cluster Discovery. In: Meidanis, J., Nakhleh, L. (eds) Comparative Genomics. RECOMB-CG 2017. Lecture Notes in Computer Science(), vol 10562. Springer, Cham. https://doi.org/10.1007/978-3-319-67979-2_11
Download citation
DOI: https://doi.org/10.1007/978-3-319-67979-2_11
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67978-5
Online ISBN: 978-3-319-67979-2
eBook Packages: Computer ScienceComputer Science (R0)