Gene discovery through comparisons of networks of structural and functional relationships among known genes and proteins
AssigneeThe Trustees of Columbia University in the City of New York
InventorsAndrey Rzhetsky, Sergey Kalachikov
Life of this patent
Estimating the term…
Abstract
The present invention relates to methods for identifying novel genes comprising: (i) generating one or more specialized databases containing information on gene/protein structure, function and/or regulatory interactions; and (ii) searching the specialized databases for homology or for a particular motif and thereby identifying a putative novel gene of interest. The invention may further comprise performing simulation and hypothesis testing to identify or confirm that the putative gene is a novel gene of interest.
Claims2
A method for identifying the affect of a gene knockout on a regulatory pathway comprising the following steps:
- (i) identification of the shortest regulatory pathway connecting two gene products;
- (ii) assigning an initial sign value of “−” to the knockout gene product;
- (iii) multiplying the initial sign value of the knockout gene product with the sign value of the adjacent gene product in the pathway, wherein “−” stands for inhibition. “+” stands for induction or activation, and “0” stands for the lack of interaction between two gene products;
- and
- (iv) determining the final sign value at the end of the pathway, wherein “−” indicates inhibition and “+” indicates induction or activation of the pathway.
A method for identifying a novel nucleic acid molecule encoding a protein of interest comprising:
- (i) selecting a gene of interest and searching a database for homologous sequences derived from one or more species;
- (ii) aligning the homologous sequences identified in step (i) with the gene of interest to form a sequence alignment;
- (iii) constructing a gene tree using the sequence alignment;
- (iv) constructing a species tree;
- (v) imputing the species tree and gene tree into an algorithm which integrates the species tree and the gene free into a reconciled tree wherein the following algorithm is used to integrate the species tree and the gene tree into a reconciled tree:
- (a) computing the similarity σ(Sgi, Ssj) for each pair of interior nodes from trees Tg and Ts,
- (b) finding the maximum σ(Sgi, Ssj);
- (c) saving Sgi as a new cluster of orthologs, save {Sgi}={Ssj} as a set of species that are likely to have gene of this kind (or lost it in evolution);
- (d) eliminating Sgi from Tg;
- Tg:=Tg\Sgi:
- (e) repeating step (ii)-(iv) until Tg is non-empty;
- (vi) identifying orthologous gene products present in one species but missing in another;
- and
- (vii) isolating a nucleic acid molecule encoding the gene products identified in step (vi) from a nucleic acid sample derived from the species in which the gene product is absent.
Dependencies are inferred from the claim text.