Co-author: Eviatar Nevo
References:
1. Bolshoy, A., P. McNamara, R.E. Harrington & E.N. Trifonov. (1991). Curved DNA without A-A: experimental estimation of all 16 DNA wedge angles. Proc Natl Acad Sci U S A 88(6), 2312-2316.
2. Gabrielian, A. and Bolshoy, A. (1999) "Sequence complexity and DNA curvature." Computers & Chemistry 23, 263-274
3. Gabrielian, A. E., Landsman, D., and Bolshoy, A. "Curved DNA in promoter
sequences" (1999) In Silico 1 4. Perez-Martin, J. & V. de Lorenzo. (1997). Clues and consequences of DNA
bending in transcription. Annu Rev Microbiol 51, 593-628.
Co-authors:
Jeanette Hargbo, Uwe H Sauer
Our method was developed specifically to
identify DNA-binding proteins with S-type immunoglobulin fold under
exclusion of common immunoglobulins. With the the X-ray structure of
the AML1 Runt domain as a starting point, we searched the PDB for
related 3D structures. Next, the 3D coordinates of the domains related
to Runt were aligned simultaneously using the Runt domain as a
template. Amino acids that were close in space among all different
protein structures were assumed to be critical for the particular fold
and were used to generate a structure based multiple sequence
alignment. From the multiple sequence alignment, a profile Hidden
Markov Model was calculated. A sequence database was searched with the
constructed profile, resulting in sequences used to generate the
profile as well as new ones that were not. Only DNA-binding
immunoglobulins were found. We predict that the proteins without known
3D structure are related to Runt and bind to DNA.
Co-authors: Miguel González and Manuel Molina
The Galton-Watson process (GWP) has often been used as a descriptive
population model (see for example Jagers(1975)). In particular, it has
been considered as a statistical model in an epidemiological context
(Becker(1975,1977), Neyman and Scott(1964),...). However, if the number
of infectives converges to a non degenerate variable and it is allowed
the incorporation of new infected individuals from other populations, the
GWP seems to be an inadequate model, being necessary to use more complex
processes. The aim of this paper is to show that for such situations it
can be considered, within the framework of the branching processes with
immigration, the study of the limit behaviour of some infectious
diseases. We present the Galton-Watson processes with immigration in an
epidemiological context and taking into account some of the factors
governing the spread of the diseases, we propose corrective policies. As
an illustration for the theoretical study, some simulated examples are
developed. The software we have used is programming language of
Mathematica (v3.0).
References:
Jagers, P.(1975) Branching processes with Biological Applications, John
Wiley, London.
Becker, N. G.(1975) The use of mathematical models in determining
vaccination policies. Bulletin of the International Statistical Institute
46, Book 1, 478-490.
Becker, N. G.(1977) Estimation for discrete time branching processes with
application to epidemics. Biometrics 33, 515-522.
Neyman, J. and Scott, E.L. (1964) Stochastic Models in Medicine and
Biology. J. Gurland editor, 45-55, University of Wisconsin Press,
Madison.
We consider a situation where the location of the gene for a
dominant disease is known. In this case, information about additional
genetic markers linked to the disease gene
can be used to estimate the age (time since appearance)
of the disease based on a sample of affected individuals. The behaviour of
this estimate is studied using simulations.
Co-authors:
Marek Kimmel, Leslea Davison, Heidi Spratt, Patrick King
References:
Kimmel, M., R. Chakraborty, J. P. King, M. Bamshad, W. S. Watkins and L.
B. Jorde, 1998. Signatures of population expansion in microsatellite
repeat data. Genetics 148: 1921-1930.
Kimmel, M., and R. Chakraborty, 1996. Measures of variation of DNA repeat
loci under a general stepwise mutation model. Theoretical Population
Biology 50: 345-367.
References: The implementation is written as a Java applet, so that students
can experiment interactively using a standard webbrowser. The source
code is fairly clear, so that students can investigate the finer
details of the implementation.
References: The algorithms can be accessed at
http://www.dina.kvl.dk/~sestoft/bsa/dinaws/bsapplet.html
Co-author:
Nickolay M. Yanev
The aim of our study is to present and investigate a new
stochastic process for modelling population dynamics, namely
Sevastyanov's age-dependent branching process with emigration.
Such model appears naturally in applications to cell populations
where with positive probability the cells may die before their
life-cycle is completed. The results may help to give answer of
such question like what one can say about the future development
of the population under certain reproduction conditions of the
individuals and rate of emigration, as well.
In this connection the use of branching processes to model
cell populations was pioneered by Bellman and Harris, where the
Bienayme-Galton-Watson branching process was generalized to a
process where each individual first lives a random amount of time,
independently of the others, and gives birth to a random number of
offspring. Further generalization of Bellman-Harris branching
process is so-called Sevastyanov's age-dependent branching process
where the progeny depends on the age of the particle at the moment
of giving birth to new particles of age zero.
Applying renewal technique we establish limit theorems in the
case when local characteristics of the processes are finite. The
limit behaviour depends essentially on the criticality of the
processes and the rate of emmigration.
References:
P. Jagers (1975) Branching Processes with biological applications.
John Wiley and Sons.
B. Sevastyanov (1971) Branching Processes. Nauka, Moscow.
M. Slavtchova-Bojkova, Multi-type Age-dependent Branching
Processes with State-dependent Immigration, Proceeedings of the
Athen's Conference on Applied Probability and Time Series
Analysis, Ed. C.C. Heyde, Yu. V. Prohorov, R. Pyke, S. T.
Rachev , Lecture Notes in Statistics, 114, p. 192-205, 1996,
Springer Verlag, New York.
Co-authors:
John Hertz, Nordita, Denmark
We present the method and show the results obtained from applying it
to both artificial and real gene expression data from developing rat
spinal cord and hippocampus. Taken together, the data from the two
tissues allow us to identify the main features of the structure of the
regulatory networks governing nervous system development.
References:
1. Wahde, M. and Hertz, J. "Coarse-grained reverse engineering of
genetic regulatory networks", Biosystems, in press
2. www.me.chalmers.se/~mwahde/genenets.html
Protein searching in the midnight zone
Karin Hardell
The aim of this work was to develop a search tool that is able to
pick out proteins with similar fold but low sequence similarity from a
sequence database. One demand is that the structure of a particular
query protein is known.
Nonparametric linkage power by simulations and multivariate normal approximation
Mikael Knutsson
Department of Mathematical Statistics, Chalmers University of
Technology, Sweden
A simulation method for generation of marker data given a specified genetic
model is presented for affected sib-pair families. We describe how powers in
nonparametric linkage analysis can be obtained, combining the marker
simulations with calculations of some appropriate linkage statistic and a
multivariate normal approximation. The approach is also used to find the
correct thresholds and pointwise levels of significance in partial genome
scans.
The Galton-Watson process with immigration in an epidemiological
context
Manuel Mota
Department of Mathematics, University of Extremadura, Spain
Estimating the age of a disease
Ulrica Olofsson
Department of Mathematical Statistics,
Göteborg University and Chalmers University of Technology,
Sweden
At some time in the past, a certain disease gene appeared in a population
by mutation. Its fate can be modelled using a multitype Galton-Watson
branching process model.
DNA Microsatellite Evolution: Facts, Theory and Simulation
Alexander Renwick
Department of Statistics, Rice University, USA
We examine length distributions of approximately 6000 human dinucleotide
microsatellite loci, representing chromosomes 1 to 22, from the GDB
Database. Under the stepwise mutation model, results from theory and
simulation are compared with the empirical data. In both constant and
expanding population scenarios, a simple single step model with parameters
chosen to account for the observed variance of microsatellite lengths
produces results inconsistent with the observed homozygosity and the
dispersion of length skewness. Complicating the model by allowing a
variable mutation rate accounts for the homozygosity, and introducing a
small probability of a large step accounts for the dispersion in
skewnesses. We discuss these results in light of the long term evolution
of microsatellites.
A Novel Approach to Structure Alignment
Markus Ringnér
Complex Systems Division, Dept. of Theoretical Physics, Lund University, Sweden
A new method for protein structure alignment is presented, which is
based on simultaneously minimizing an error function with respect to
both assignment and structural degrees of freedom. The assignment part
is minimized using a deterministic mean field approach. The latter
implicitly enables exploration of the entire space of possible
alignments and is hence able to handle permutations. Also, it allows
for a probabilistic interpretation of the results. The method is
extremely generic and can conveniently host a variety of constraints
in addition to matching. It performs very well including situations,
where permutations are called for.
M. Ohlsson, C. Peterson, M. Ringnér and R. Blancenbecler
A Novel Approach to Structure Alignment
LU TP 00-07 and SLAC-PUB-8429 (2000)
A pedagogical implementation of biosequence alignment algorithms
Peter Sestoft
Department of Mathematics and Physics, Royal Veterinary and
Agricultural University, Denmark
We present a model implementation of the standard dynamic programming
algorithms for biosequence alignment: global alignment
(Needleman-Wunsch), local alignment (Smith-Waterman), overlap
alignment, repeated matches. We handle linear as well as affine gap
costs, and implement the (simple) quadratic-space as well as the
(slightly more complicated) linear-space versions of the dynamic
programming algorithms.
Branching processes with emigration for modelling cell populations
Marossia N. Slavtchova-Bojkova
Department of Probability and Statistics,
Bulgarian Academy of Sciences
Non-linear modeling of genetic regulatory interactions
Mattias Wahde
Div. of Mechatronics, Chalmers University of Technology,
Sweden
The availability of time series of gene expression data has made
possible the investigation of interactions between genes of groups
of genes. We have studied genetic regulatory networks using a
(non-linear) recurrent network model. Using evolutionary algorithms,
we have developed a method for determining the interactions
in such networks.
Last modified: Sun May 7 14:10:42 MET DST 2000