Research Highlights

Jeremy Buhler and Martin Tompa received the RECOMB 2013 Test of Time Award for their 2001 publication "Finding motifs using random projections". That work introduced a novel randomized algorithm for the discovery of short sequence motifs such as transcription factor binding sites, remedying weaknesses observed in existing motif discovery algorithms and solving difficult motif challenge problems that had been posed by Pevzner and Sze.

 
Associated Faculty:
Associated Publications:
  • J. Buhler, "Provably sensitive indexing strategies for biosequence similarity search", J. Comput. Biol., vol. 10 (2003) 399-417. Pubmed 13677335.   Supplement.
  • J. Buhler, M. Tompa, "Finding motifs using random projections", J. Comput. Biol., vol. 9 (2002) 225-42. Pubmed 12015879.   Supplement.

Georg Seelig has received a 2011 Alfred P. Sloan Research Fellowship, among the most selective awards for young scientists.

Seelig, a synthetic biologist, joined CSE and EE in 2009. He received a Diploma in Physics from the University of Basel in 1999 and a Ph.D. in theoretical physics from the University of Geneva in 2003. Before coming to UW he was a postdoc at Caltech working with Erik Winfree and Michael Elowitz. He is interested in understanding how biological organisms process information using complex biochemical networks, and how such networks can be engineered to program cellular behavior. Engineered circuits and circuit elements are being applied to problems in disease diagnostics and therapy.

CSE's Anup Rao also won a Sloan Fellowship; the two join 15 UW CSE faculty members so-honored in previous years.

 
Associated Faculty:
Associated Publications:
  • D. Zhang, G. Seelig, "Dynamic DNA nanotechnology using strand-displacement reactions", Nat Chem, vol. 3 (2011) 103-13. Pubmed 21258382.

The programmable and reliable hybridization of DNA strands has enabled the preparation of a wide variety of structures. This Review discusses how, in addition to these static assemblies, the process of displacing — and ultimately replacing — strands also makes possible the construction of dynamic systems such as logic gates and autonomous walkers.

 
Associated Faculty:
Associated Publications:
  • D. Zhang, G. Seelig, "Dynamic DNA nanotechnology using strand-displacement reactions", Nat Chem, vol. 3 (2011) 103-13. Pubmed 21258382.

Huei-Hun Elizabeth Tseng's poster "A Digital Fingerprinting method for screening the gut microbiome across human populations" won the Best Student Poster prize at Beyond the Genome 2010 in October. The project concerns a high-tech approach to measuring the diversity of microbes resident in the human gut.

The human microbiome is increasingly recognized as an important factor in human health, yet the lack of cost-effective profiling techniques has prohibited broad human population studies linking variation in gut microbiome diversity to variation in disease risk. Tseng and collaborators are developing a Digital Fingerprinting technique to discriminate the gut bacterial community among individuals while capturing the microbial diversity. With the advent of sequencers that provide high-throughput sequencing at more affordable cost, Digital Fingerprinting can serve as an effective diagnostic tool or an initial screening tool for grouping samples according to disease or condition.

Collaborators include Meredith Hullar, Fei Li, and Johanna W. Lampe from the Fred Hutchinson Cancer Research Center, Lisa Strate from UW Gastroenterology, and Richard Sandstrom, Audra K. Johnson, and John Stamatoyonnopoulos from Genome Sciences.

 

Imagery of motor movement plays an important role in learning complex motor skills. In the February 2010 issue of the Proceedings of the National Academy of Sciences, members of the Neural Systems Laboratory measured electrocorticographic cortical surface potentials in eight human subjects during overt action and kinesthetic imagery of the same movement. They established that the spatial distribution of local neuronal population activity during motor imagery mimics the spatial distribution of activity during actual motor movement. By comparing responses to electrocortical stimulation with imagery-induced cortical surface activity, they demonstrated the role of primary motor areas in movement imagery.

 
Associated Faculty:

In chemistry and biology, the formalism of mass action equations is commonly used to model and understand the time evolution of complex molecular systems. In a typical application we are given a system of interacting molecules and then try to build a chemical reaction model based on that knowledge. In this paper, we take the opposite approach and ask, "Given a formal chemical reaction network (CRN) with a desired dynamical behavior, can we find molecules that implement this behavior?" We argue that this is in fact possible, and propose a specific DNA-based implementation for arbitrary CRN. In our approach, the formalism of CRNs becomes a prescriptive "programming language" rather than a descriptive modeling language.

As one anonymous reviewer explained: “[This work] sets on a proper foundation the hundreds – perhaps thousands – of papers that have been published on the dynamics of CRNs... [T]here have been many instances where new mathematics and new design ideas were recognized as interesting, but were also criticized on the grounds that they were vapid: ‘How do you know that chemical reactions with these properties even exist?’ This paper proves that every chemical reaction network exists.”

 
Associated Faculty:
Associated Publications:
  • D. Soloveichik, G. Seelig, E. Winfree, "DNA as a universal substrate for chemical kinetics", Proc. Natl. Acad. Sci. U.S.A., vol. 107 (2010) 5393-8. Pubmed 20203007.

Predicting a stable three-dimensional structure from any given amino acid sequence using first physical principles remains a formidable computational challenge. Aiming to recruit human visual and strategic powers to the task, Zoran Popović, David Baker, and colleagues created an online multiplayer game called Foldit, in which thousands of nonscientists compete and collaborate to produce a rich set of search strategies for protein structure refinement. This work, published in the August 2010 issue of Nature, shows that even computationally complex scientific problems can be effectively crowd-sourced using interactive multiplayer games.

 
Associated Faculty:

In the June 2010 issue of Nature Biotechnology, Xiaoyu Chen and Martin Tompa assessed four expert ENCODE alignments, each of which aligns 28 vertebrate sequences on 554,000,000 base-pairs of total input sequence. They reported a disturbing lack of agreement among the alignments not only in species distant from human, but even in mouse, a well-studied model organism. Overall, the assessment showed that the Pecan alignment method produced the most accurate or nearly most accurate alignment in all species and genomic location categories, while still providing coverage comparable to or better than that of the other alignments.

 
Associated Faculty:

In the textbooks, genes are controlled by transcription factors, proteins that bind to DNA near the starts of genes to activate or repress them. One of the best-studied transcription factors, called MyoD, is a master regulator of myogenesis, the process by which precursor cells differentiate into skeletal muscle cells. Indeed, expressing this one protein in a fibroblast (skin cell) causes extensive remodeling of the cell, resulting in a facsimile of a muscle cell. Walter L. Ruzzo and collaborators at the Fred Hutchinson Cancer Research Center have assayed genome-wide MyoD binding in differentiating and mature muscle cells, adding greatly to our understanding of these processes. They used "ChIP-seq" technology -- Chromatin ImmunoPrecipitation followed by next-gen sequencing. As expected, MyoD is found near start sites of the several hundred genes that are known to be driven by this powerful regulator. Surprisingly, however, these sites comprise only a tiny fraction of the sites bound by MyoD, many thousands of which occur far from any gene. These data suggest that MyoD is unexpectedly multifunctional, initiating changes in chromatin state that result in broad "reprogramming" of the cell, in addition to its canonical role in activating genes immediately adjacent to some of its target sites. Read the full article or the short accompanying comment in Developmental Cell, both cited below.

 
Associated Faculty:
Associated Publications:
  • M. Biggin, "MyoD, a lesson in widespread DNA binding", Dev. Cell, vol. 18 (2010) 505-6. Pubmed 20412764.
  • Y. Cao, Z. Yao, D. Sarkar, M. Lawrence, G. Sanchez, M. Parker, K. MacQuarrie, J. Davison, M. Morgan, W. Ruzzo, R. Gentleman, S. Tapscott, "Genome-wide MyoD binding in skeletal muscle cells: a potential for broad cellular reprogramming", Dev. Cell, vol. 18 (2010) 662-74. Pubmed 20412780.   Supplement.