30,699 research outputs found
Network estimation in State Space Model with L1-regularization constraint
Biological networks have arisen as an attractive paradigm of genomic science
ever since the introduction of large scale genomic technologies which carried
the promise of elucidating the relationship in functional genomics. Microarray
technologies coupled with appropriate mathematical or statistical models have
made it possible to identify dynamic regulatory networks or to measure time
course of the expression level of many genes simultaneously. However one of the
few limitations fall on the high-dimensional nature of such data coupled with
the fact that these gene expression data are known to include some hidden
process. In that regards, we are concerned with deriving a method for inferring
a sparse dynamic network in a high dimensional data setting. We assume that the
observations are noisy measurements of gene expression in the form of mRNAs,
whose dynamics can be described by some unknown or hidden process. We build an
input-dependent linear state space model from these hidden states and
demonstrate how an incorporated regularization constraint in an
Expectation-Maximization (EM) algorithm can be used to reverse engineer
transcriptional networks from gene expression profiling data. This corresponds
to estimating the model interaction parameters. The proposed method is
illustrated on time-course microarray data obtained from a well established
T-cell data. At the optimum tuning parameters we found genes TRAF5, JUND, CDK4,
CASP4, CD69, and C3X1 to have higher number of inwards directed connections and
FYB, CCNA2, AKT1 and CASP8 to be genes with higher number of outwards directed
connections. We recommend these genes to be object for further investigation.
Caspase 4 is also found to activate the expression of JunD which in turn
represses the cell cycle regulator CDC2.Comment: arXiv admin note: substantial text overlap with arXiv:1308.359
A generalized risk approach to path inference based on hidden Markov models
Motivated by the unceasing interest in hidden Markov models (HMMs), this
paper re-examines hidden path inference in these models, using primarily a
risk-based framework. While the most common maximum a posteriori (MAP), or
Viterbi, path estimator and the minimum error, or Posterior Decoder (PD), have
long been around, other path estimators, or decoders, have been either only
hinted at or applied more recently and in dedicated applications generally
unfamiliar to the statistical learning community. Over a decade ago, however, a
family of algorithmically defined decoders aiming to hybridize the two standard
ones was proposed (Brushe et al., 1998). The present paper gives a careful
analysis of this hybridization approach, identifies several problems and issues
with it and other previously proposed approaches, and proposes practical
resolutions of those. Furthermore, simple modifications of the classical
criteria for hidden path recognition are shown to lead to a new class of
decoders. Dynamic programming algorithms to compute these decoders in the usual
forward-backward manner are presented. A particularly interesting subclass of
such estimators can be also viewed as hybrids of the MAP and PD estimators.
Similar to previously proposed MAP-PD hybrids, the new class is parameterized
by a small number of tunable parameters. Unlike their algorithmic predecessors,
the new risk-based decoders are more clearly interpretable, and, most
importantly, work "out of the box" in practice, which is demonstrated on some
real bioinformatics tasks and data. Some further generalizations and
applications are discussed in conclusion.Comment: Section 5: corrected denominators of the scaled beta variables (pp.
27-30), => corrections in claims 1, 3, Prop. 12, bottom of Table 1. Decoder
(49), Corol. 14 are generalized to handle 0 probabilities. Notation is more
closely aligned with (Bishop, 2006). Details are inserted in eqn-s (43); the
positivity assumption in Prop. 11 is explicit. Fixed typing errors in
equation (41), Example
A Mutagenetic Tree Hidden Markov Model for Longitudinal Clonal HIV Sequence Data
RNA viruses provide prominent examples of measurably evolving populations. In
HIV infection, the development of drug resistance is of particular interest,
because precise predictions of the outcome of this evolutionary process are a
prerequisite for the rational design of antiretroviral treatment protocols. We
present a mutagenetic tree hidden Markov model for the analysis of longitudinal
clonal sequence data. Using HIV mutation data from clinical trials, we estimate
the order and rate of occurrence of seven amino acid changes that are
associated with resistance to the reverse transcriptase inhibitor efavirenz.Comment: 20 pages, 6 figure
MRFalign: Protein Homology Detection through Alignment of Markov Random Fields
Sequence-based protein homology detection has been extensively studied and so
far the most sensitive method is based upon comparison of protein sequence
profiles, which are derived from multiple sequence alignment (MSA) of sequence
homologs in a protein family. A sequence profile is usually represented as a
position-specific scoring matrix (PSSM) or an HMM (Hidden Markov Model) and
accordingly PSSM-PSSM or HMM-HMM comparison is used for homolog detection. This
paper presents a new homology detection method MRFalign, consisting of three
key components: 1) a Markov Random Fields (MRF) representation of a protein
family; 2) a scoring function measuring similarity of two MRFs; and 3) an
efficient ADMM (Alternating Direction Method of Multipliers) algorithm aligning
two MRFs. Compared to HMM that can only model very short-range residue
correlation, MRFs can model long-range residue interaction pattern and thus,
encode information for the global 3D structure of a protein family.
Consequently, MRF-MRF comparison for remote homology detection shall be much
more sensitive than HMM-HMM or PSSM-PSSM comparison. Experiments confirm that
MRFalign outperforms several popular HMM or PSSM-based methods in terms of both
alignment accuracy and remote homology detection and that MRFalign works
particularly well for mainly beta proteins. For example, tested on the
benchmark SCOP40 (8353 proteins) for homology detection, PSSM-PSSM and HMM-HMM
succeed on 48% and 52% of proteins, respectively, at superfamily level, and on
15% and 27% of proteins, respectively, at fold level. In contrast, MRFalign
succeeds on 57.3% and 42.5% of proteins at superfamily and fold level,
respectively. This study implies that long-range residue interaction patterns
are very helpful for sequence-based homology detection. The software is
available for download at http://raptorx.uchicago.edu/download/.Comment: Accepted by both RECOMB 2014 and PLOS Computational Biolog
- …