## Identifying Gene Regulatory Networks from Experimental Data (1999)

Citations: | 48 - 4 self |

### BibTeX

@INPROCEEDINGS{Chen99identifyinggene,

author = {Ting Chen and Vladimir Filkov and Steven S. Skiena},

title = {Identifying Gene Regulatory Networks from Experimental Data},

booktitle = {},

year = {1999},

pages = {94--103},

publisher = {ACM Press}

}

### Years of Citing Articles

### OpenURL

### Abstract

this paper, we propose a methodology for making sense of large, multiple time-series data sets arising in expression analysis, and evaluate it both theoretically and through a case study. First, we build a graph representing all putative activation/inhibition relationships by analyzing the expression profiles for all pairs of genes. Second, we prune this graph by solving a combinatorial optimization problem to identify a small set of interesting candidate regulatory elements. We do not assert that we identify "the" regulatory network as a result of this computation. However, we believe that our approach quickly enables biologists to identify and visualize interesting features from raw expression array data sets. We have implemented our methodology and applied it to the analysis of the Saccharomyces cerevisiae data set. In this paper, we report on our implementation and the results of our data analysis. The problem of inducing gene regulation networks has recently come to the computational biology community. Initial attempts at modeling gene expression abd programs to induce regulatory networks from data include [2, 10, 13]. To take fullest advantage of laboratory experiments that can be performed in which a given set of genes can be explicitly expressed or repressed, and the consequences of these genes on expression biologically determined, Akutsu, et.al. [1] considers the problem of designing a minimum-size series of experiments guaranteed to result in the identification of the correct regulatory network. The candidate regulatory network proposed by our system depends upon the specific optimization criteria employed in the second phase of our procedure, although our experiments suggest that the optimal network is surprisingly robust to changes in the objective function...

### Citations

11366 |
Computers and Intractability: A Guide to the Theory of NP-Completeness
- Garey, Johnson
- 1979
(Show Context)
Citation Context ... that all the vertices with nonzero indegree can be satisfied if and only if the original boolean formula is satisfiable. Since 3-SAT remains hard even if no literal appears in more than five clauses =-=[5]-=-, gene regulation remains hard if each vertex has outdegree at most 7 and indegree at most 4. 4.2 Approximability In this section, we consider two classes of randomized approximation algorithms for th... |

2292 |
Dubes, “Algorithms for clustering data
- Jain, C
- 1988
(Show Context)
Citation Context ...fficient of the profiles as a similarity measure. We set a lower bound of 0.85 below which we didn't allow two different clusters to merge. We used the well-known average linkage method of clustering =-=[8]-=-, where each of the clusters was identified by an average, or consensus, function, at any point during the execution of the algorithm. This consensus was obtained as an average of all the ORFs that be... |

700 |
Exploring the metabolic and genetic control of gene expression on a genomic scale
- Risi, Iyer, et al.
- 1997
(Show Context)
Citation Context ... Model for Analyzing Expression Data Our approach begins with a data set monitoring the expression level of each gene as a function of time. Such data sets are now becoming available. J. DeRisi et.al =-=[4]-=- recently made public a seven-point time series dataset for each gene in Saccharomyces cerevisiae. An even better dataset, with 17 sample points per gene, has been produced by Cho, et.al [3] and is th... |

378 |
A genome-wide transcriptional analysis of the mitotic cell cycle
- Cho, Campbell, et al.
- 1998
(Show Context)
Citation Context ...gonucleotide arrays [11] and micro arrays) now make it possible to quickly obtain vast amounts of data on gene expression in a particular organism under particular conditions. For example, Cho, et.al =-=[3]-=- recently published a 17-point time series data set measuring the expression level of each of 6601 different genes for the yeast Saccharomyces cerevisiae, obtained using an Affymetrix hybridization ar... |

261 | REVEAL, A General Reverse Engineering Algorithm for Inference of Genetic Network Architectures
- Liang, Fuhrman, et al.
- 1998
(Show Context)
Citation Context ...f inducing gene regulation networks has recently come to the computational biology community. Initial attempts at modeling gene expression abd programs to induce regulatory networks from data include =-=[2, 10, 13]-=-. To take fullest advantage of laboratory experiments that can be performed in which a given set of genes can be explicitly expressed or repressed, and the consequences of these genes on expression bi... |

185 | Modeling gene expression with differential equations
- Chen, He, et al.
- 1999
(Show Context)
Citation Context ...f inducing gene regulation networks has recently come to the computational biology community. Initial attempts at modeling gene expression abd programs to induce regulatory networks from data include =-=[2, 10, 13]-=-. To take fullest advantage of laboratory experiments that can be performed in which a given set of genes can be explicitly expressed or repressed, and the consequences of these genes on expression bi... |

152 |
Large-scale temporal gene expression mapping of central nervous system development
- Wen, Fuhrman
- 1998
(Show Context)
Citation Context ...hed a 17-point time series data set measuring the expression level of each of 6601 different genes for the yeast Saccharomyces cerevisiae, obtained using an Affymetrix hybridization array. Wen, et.al =-=[16]-=- has generated 9-point times series for the expression levels using RT-PCR of each of 112 genes involved in the rat nervous system development. Associating functions to genes based on this huge amount... |

79 | Algorithms for clustering data. PrenticeHall advanced reference series. Upper Saddle River - Jain, Dubes - 1988 |

71 | New 3/4-approximation algorithms for the maximum satisfiability problem
- Goemans, Williamson
- 1994
(Show Context)
Citation Context ...ization problems follow from solving a linear or semidefinite programming relaxation, and then rounding the optimized solutions into integer solutions for the original problem. Goemans and Williamson =-=[6]-=- first used positive linear programming relaxation to give a 3/4-approximation algorithm for maximum satisfiability, and later [7] improved the factor to 0.758 by using semidefinite programming relaxa... |

67 | Identification of gene regulatory networks by strategic gene disruptions and gene overexpressions
- Akutsu, Kuhara, et al.
- 1998
(Show Context)
Citation Context ...ory experiments that can be performed in which a given set of genes can be explicitly expressed or repressed, and the consequences of these genes on expression biologically determined, Akutsu, et.al. =-=[1]-=- considers the problem of designing a minimum-size series of experiments guaranteed to result in the identification of the correct regulatory network. The candidate regulatory network proposed by our ... |

45 | Qualitative analysis of gene networks
- Thieffry, Thomas
- 1998
(Show Context)
Citation Context ...f inducing gene regulation networks has recently come to the computational biology community. Initial attempts at modeling gene expression abd programs to induce regulatory networks from data include =-=[2, 10, 13]-=-. To take fullest advantage of laboratory experiments that can be performed in which a given set of genes can be explicitly expressed or repressed, and the consequences of these genes on expression bi... |

28 |
The Minimum Satisfiability Problem
- Kohli, Khrishnamurti, et al.
- 1994
(Show Context)
Citation Context ...atisfied clauses, where both literals must be true to satisfy a clause. Lemma 8 Restricted maximum 2-of-2-SAT is NP-complete. Proof: Maximum 2-SAT and minimum 2-SAT are wellknown NP-complete problems =-=[9]. The ha-=-rdness of maximum 2-of-2-SAT follows by a simple reduction from minimum 2-SAT, where both literals of each clause (x; y) is converted into the clause (��x; �� y). Needing both x and y to satis... |

23 | Positive linear programming, parallel approximation and pcps
- Trevisan
(Show Context)
Citation Context ...pproximation to maximum gene regulation, when p = 2=3. Corollary 1 is not the best result possible -- we note that a factor 1/2 approximation algorithm for indegree 2 networks follows from Trevisan's =-=[14]-=- factor 2 1\Gammak approximation of maximum k conjunctive satisfiability. However, Lemma 2 can be used to generalize our assignment to arbitrary degree gene regulatory networks. Since any vertex witho... |

19 |
An O( (jV j)jEj) algorithm for finding maximum matching in general graphs
- Micali, Vazirani
- 1980
(Show Context)
Citation Context ... it can be solved in linear time when each gene has indegree and outdegree of at most two. Proof: By Lemma 6, we have reduced this problem to maximum cardinality matching in D(G). Micali and Vazirani =-=[12]-=- find maximum matchings in O( p nm) time. The result follows since dual graph contains O(n) edges. For the indegree 2 case, observe that each vertex in D(G) must have degree at most two when each vert... |

16 | Approximating satisfiable satisfiability problems
- Trevisan
(Show Context)
Citation Context ...itive linear programming relaxation to give a 3/4-approximation algorithm for maximum satisfiability, and later [7] improved the factor to 0.758 by using semidefinite programming relaxation. Trevisan =-=[15]-=- gives a 2 1\Gammak -approximation algorithm for MAX k CONJ SAT problem. Here we show that maximum gene regulation can be approximated to a 1/2 factor using positive linear programming relaxation. Let... |

10 | Identi� cation of gene regulatory networks by strategic gene disruptions and gene over-expressions - Akutsu, Kuhara, et al. - 1998 |

4 | The minimum satis ability problem - Kohli, Krishnamurti, et al. - 1994 |

3 |
Expression monitoring by hybrdiziation to highdensity oligonucleotide arrays
- Lockhart, Dong, et al.
- 1996
(Show Context)
Citation Context ...ducts. Identifying gene regulatory networks from experimental data is now an area of extremely active research. New experimental technologies in molecular biology (particularly oligonucleotide arrays =-=[11]-=- and micro arrays) now make it possible to quickly obtain vast amounts of data on gene expression in a particular organism under particular conditions. For example, Cho, et.al [3] recently published a... |

3 | Modeling gene expression with di erential equations - Chen, He, et al. - 1999 |

1 |
Improved approxiamtion algorithms for maximum cut and satis ability problems using semide nite programming
- Goemans, Williamson
- 1995
(Show Context)
Citation Context ...to integer solutions for the original problem. Goemans and Williamson [6] first used positive linear programming relaxation to give a 3/4-approximation algorithm for maximum satisfiability, and later =-=[7]-=- improved the factor to 0.758 by using semidefinite programming relaxation. Trevisan [15] gives a 2 1\Gammak -approximation algorithm for MAX k CONJ SAT problem. Here we show that maximum gene regulat... |

1 | An O( p jV jjej) algorithm for nding maximum matchings in general graphs - Micali, Vazirani - 1980 |

1 | Approximating satis able satis ability problems - Trevisan - 1997 |