Gene discovery through comparisons of networks of structural and functional relationships among known genes and proteins

A method for identifying the affect of a gene knockout on a regulatory pathway comprising the following steps:

• (i) identification of the shortest non-oriented pathway connecting two gene products;
• (ii) assigning an initial sign value of “−” to the knockout since the knockout gene product is inactive;
• (iii) moving along the shortest pathway between the two gene products multiplying the sign with the sign of the next gene product in the pathway, wherein “−” stands for inhibition, “+” stands for induction or activation, and “0” stands for the lack of interaction between two proteins in the specified direction;
• and
• (iv) determining the final sign 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;
• (ii) aligning the homologous sequences identified in step (i);
• (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 tree into a reconciled tree;
• and
• (vi) identifying orthologous genes present in one species but missing in another.

A method for identifying a novel gene comprising the following steps:

• (i) defining a motif or domain composition of a gene of interest;
• (ii) searching for sequences which correspond to nucleotide sequences in an expression sequence tag database or other cDNA databases using a program such as BLAST and retrieving the identified sequences;
• (iii) searching additional databases for expressed sequence tags containing the domains and motifs characteristic for the gene of interest with Hidden Markov Model of domains and motifs identified in step (i);
• (iv) identifying nucleotide sequences comprising the gene of interest.