162 research outputs found
Understanding Health and Disease with Multidimensional Single-Cell Methods
Current efforts in the biomedical sciences and related interdisciplinary
fields are focused on gaining a molecular understanding of health and disease,
which is a problem of daunting complexity that spans many orders of magnitude
in characteristic length scales, from small molecules that regulate cell
function to cell ensembles that form tissues and organs working together as an
organism. In order to uncover the molecular nature of the emergent properties
of a cell, it is essential to measure multiple cell components simultaneously
in the same cell. In turn, cell heterogeneity requires multiple cells to be
measured in order to understand health and disease in the organism. This review
summarizes current efforts towards a data-driven framework that leverages
single-cell technologies to build robust signatures of healthy and diseased
phenotypes. While some approaches focus on multicolor flow cytometry data and
other methods are designed to analyze high-content image-based screens, we
emphasize the so-called Supercell/SVM paradigm (recently developed by the
authors of this review and collaborators) as a unified framework that captures
mesoscopic-scale emergence to build reliable phenotypes. Beyond their specific
contributions to basic and translational biomedical research, these efforts
illustrate, from a larger perspective, the powerful synergy that might be
achieved from bringing together methods and ideas from statistical physics,
data mining, and mathematics to solve the most pressing problems currently
facing the life sciences.Comment: 25 pages, 7 figures; revised version with minor changes. To appear in
J. Phys.: Cond. Mat
Probing Noise in Gene Expression and Protein Production
We derive exact solutions of simplified models for the temporal evolution of
the protein concentration within a cell population arbitrarily far from the
stationary state. We show that monitoring the dynamics can assist in modeling
and understanding the nature of the noise and its role in gene expression and
protein production. We introduce a new measure, the cell turnover distribution,
which can be used to probe the phase of transcription of DNA into messenger
RNA.Comment: 10 pages, 3 figures, supplementary information on reques
Shapes of hydrophobic thick membranes
We introduce and study the behavior of a tethered membrane of non-zero
thickness embedded in three dimensions subject to an effective self-attraction
induced by hydrophobicity arising from the tendency to minimize the area
exposed to a solvent. The phase behavior and the nature of the folded
conformations are found to be quite distinct in the small and large solvent
size regimes. We demonstrate spontaneous symmetry-breaking with the membrane
folding along a preferential axis, when the solvent molecules are small
compared to the membrane thickness. For large solvent molecule size, a local
crinkling mechanism effectively shields the membrane from the solvent, even in
relatively flat conformations. We discuss the binding/unbinding transition of a
membrane to a wall that serves to shield the membrane from the solvent.Comment: 7 pages, 5 figures, to appear in EP
Variational approach to protein design and extraction of interaction potentials
We present and discuss a novel approach to the direct and inverse protein
folding problem. The proposed strategy is based on a variational approach that
allows the simultaneous extraction of amino acid interactions and the
low-temperature free energy of sequences of amino acids. The knowledge-based
technique is simple and straightforward to implement even for realistic
off-lattice proteins because it does not entail threading-like procedures. Its
validity is assessed in the context of a lattice model by means of a variety of
stringent checks.Comment: 5 pages, 3 figure
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