Papers by Henrik Flyvbjerg
Proceedings of the National Academy of Sciences of the United States of America, Oct 30, 2018
To elucidate cellular diversity and clonal evolution in tissues and tumors, one must resolve geno... more To elucidate cellular diversity and clonal evolution in tissues and tumors, one must resolve genomic heterogeneity in single cells. To this end, we have developed low-cost, mass-producible micro-/nanofluidic chips for DNA extraction from individual cells. These chips have modules that collect genomic DNA for sequencing or map genomic structure directly, on-chip, with denaturation-renaturation (D-R) optical mapping [Marie R, et al. (2013) 110:4893-4898]. Processing of single cells from the LS174T colorectal cancer cell line showed that D-R mapping of single molecules can reveal structural variation (SV) in the genome of single cells. In one experiment, we processed 17 fragments covering 19.8 Mb of the cell's genome. One megabase-large fragment aligned well to chromosome 19 with half its length, while the other half showed variable alignment. Paired-end single-cell sequencing supported this finding, revealing a region of complexity and a 50-kb deletion. Sequencing struggled, howev...
The European Physical Journal Special Topics
Given a theoretical model for a self-propelled particle or microorganism , how does one optimally... more Given a theoretical model for a self-propelled particle or microorganism , how does one optimally determine the parameters of the model from experimental data in the form of a time-lapse recorded trajectory? For very long trajectories, one has very good statistics, and optimality may matter little. However, for biological microorganisms , one may not control the duration of recordings, and then optimality can matter. This is especially the case if one is interested in individuality and hence cannot improve statistics by taking population averages over many trajectories. One can learn much about this problem by studying its simplest case, pure diffusion with no self-propagation. This is an interesting problem also in its own right for the very same reasons: interest in individuality and short trajectories. We summarize our recent results on this latter issue here and speculate about the extent to which similar results may be obtained also for self-propelled particles.
Biomathematics. Mathematics of Biostructures and Biodynamics, edited by S. Andersson, K. Larsson, M. Larsson and M. Jacob, Elsevier, Amsterdam, 1999. www.elsevier.nl and www.elsevier.com. ISBN: 0-444-50273-4, 536 pp; US$215.50
Chem Phys Lipids, 2000
Designing optimal spatial filters for single-trial EEG classification in a movement task
We devised spatial filters for multi-channel EEG that lead to signals which discriminate optimall... more We devised spatial filters for multi-channel EEG that lead to signals which discriminate optimally between two conditions. We demonstrate the effectiveness of this method by classifying single-trial EEGs, recorded during preparation for movements of the left or right index finger or the right foot. The classification rates for 3 subjects were 94, 90 and 84%, respectively. The filters are estimated from a set of multichannel EEG data by the method of Common Spatial Patterns, and reflect the selective activation of cortical areas. By construction, we obtain an automatic weighting of electrodes according to their importance for the classification task. Computationally, this method is parallel by nature, and demands only the evaluation of scalar products. Therefore, it is well suited for on-line data processing. The recognition rates obtained with this relatively simple method are as good as, or higher than those obtained previously with other methods. The high recognition rates and the method's procedural and computational simplicity make it a particularly promising method for an EEG-based brain-computer interface.
Antigen microarray data files
Physical Review E, 2016
We determine the nonuniform stretching of and tension in a mega base pairs-long fragment of deoxy... more We determine the nonuniform stretching of and tension in a mega base pairs-long fragment of deoxyribonucleic acid (DNA) that is flow stretched in a nanofluidic chip. We use no markers, do not know the contour length of the DNA, and do not have the full DNA molecule inside our field of view. Instead, we analyze the transverse thermal motion of the DNA. Tension at the center of the DNA adds up to 16 pN, giving almost fully stretched DNA. This method was devised for optical mapping of DNA, specifically, DNA denaturation patterns. It may be useful also for other studies, e.g., DNA-protein interactions, specifically, their tension dependence. Generally, wherever long strands of DNA-e.g., native DNA extracted from human cells or bacteria-must be stretched with ease for inspection, this method applies.
Interpolating between O(N)-symmetric sigma-models with N = 1,2,3
Nucl Phys B Proc Suppl, 1991
We interpolate between the O(N)- and the O(N - 1)-symmetric non-linear sigma-models with standard... more We interpolate between the O(N)- and the O(N - 1)-symmetric non-linear sigma-models with standard action by suppressing the Nth component of the N-vector field with a mass term. We find a critical line in the coupling-mass plane connecting the critical point of the Ising model (N = 1) with the critical point of the XY-model (N = 2). This line extends towards the region of non-monotonous behaviour of the ß-function of the O(3)-symmetric model. The massless phase of the XY-model is separated from the ordered phase of the Ising model by a transition at zero mass, while it is separated from the only phase of the O(3)-model by a transition that seems to occur at exponentially small mass.
The derivation of Marko and Siggia's interpolation formula for the force-extension relation of th... more The derivation of Marko and Siggia's interpolation formula for the force-extension relation of the Worm-Like Chain Model (C.
1/N-expansions of s-models in 2 and 4 dimensions: Taking them to their technical limits
Nucl Phys B Proc Suppl, 1991
Bioinformatics (Oxford, England), 2015
Next-generation sequencing produces vast amounts of data with errors that are difficult to distin... more Next-generation sequencing produces vast amounts of data with errors that are difficult to distinguish from true biological variation when coverage is low. We demonstrate large reductions in error frequencies, especially for high-error-rate reads, by three independent means: (i) filtering reads according to their expected number of errors, (ii) assembling overlapping read pairs and (iii) for amplicon reads, by exploiting unique sequence abundances to perform error correction. We also show that most published paired read assemblers calculate incorrect posterior quality scores. These methods are implemented in the USEARCH package. Binaries are freely available at http://drive5.com/usearch. [email protected] Supplementary data are available at Bioinformatics online.
Journal of Micromechanics and Microengineering, 2015
We demonstrate all-polymer injection molded devices for optical mapping of denaturationrenaturati... more We demonstrate all-polymer injection molded devices for optical mapping of denaturationrenaturation (DR) patterns on long, single DNA-molecules from the human genome. The devices have channels with ultra-low aspect ratio, only 110 nm deep while 20 μm wide, and are superior to the silica devices used previously in the field. With these polymer devices, we demonstrate on-chip recording of DR images of DNA-molecules stretched to more than 95% of their contour length. The stretching is done by opposing flows Marie et al (2013 Proc. Natl Acad. Sci. USA 110 4893-8). The performance is validated by mapping 20 out of 24 Mbp-long DNA fragments to the human reference genome. We optimized fabrication of the devices to a yield exceeding 95%. This permits a substantial economies-of-scale driven cost-reduction, leading to device costs as low as 3 USD per device, about a factor 70 lower than the cost of silica devices. This lowers the barrier to a wide use of DR mapping of native, megabase-size DNA molecules, which has a huge potential as a complementary method to next-generation sequencing.
Nature communications, Jan 4, 2015
Molecular motors are responsible for numerous cellular processes from cargo transport to heart co... more Molecular motors are responsible for numerous cellular processes from cargo transport to heart contraction. Their interactions with other cellular components are often transient and exhibit kinetics that depend on load. Here, we measure such interactions using 'harmonic force spectroscopy'. In this method, harmonic oscillation of the sample stage of a laser trap immediately, automatically and randomly applies sinusoidally varying loads to a single motor molecule interacting with a single track along which it moves. The experimental protocol and the data analysis are simple, fast and efficient. The protocol accumulates statistics fast enough to deliver single-molecule results from single-molecule experiments. We demonstrate the method's performance by measuring the force-dependent kinetics of individual human β-cardiac myosin molecules interacting with an actin filament at physiological ATP concentration. We show that a molecule's ADP release rate depends exponentiall...
Physical review letters, Jan 15, 2015
We demonstrate that a microfabricated bump array can concentrate genomic-length DNA molecules eff... more We demonstrate that a microfabricated bump array can concentrate genomic-length DNA molecules efficiently at continuous, high flow velocities, up to 40 μm/s, if the single-molecule DNA globule has a sufficiently large shear modulus. Increase in the shear modulus is accomplished by compacting the DNA molecules to minimal coil size using polyethylene glycol (PEG) derived depletion forces. We map out the sweet spot, where concentration occurs, as a function of PEG concentration and flow speed using a combination of theoretical analysis and experiment. Purification of DNA from enzymatic reactions for next-generation DNA-sequencing libraries will be an important application of this development.
Making waves–How can waves of hydrogen peroxide transmit intracellular information in plant cells?
Micro-and macro-canonical ensembles and the Boltzmann distribution (guest lecture)
Error estimation on correlated data
1/N-expansion of the N-component φ 4 theory in 4 dimensions
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Papers by Henrik Flyvbjerg