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Conserved Domain C ombination In Protein Interaction

Conserved Domain C ombination In Protein Interaction. Jung, Suk Hoon. October 16, 2009. Contents. Background Conserved Domain Combination GO term evaluation Evaluation on Primary DC for Protein Interaction Discussion. Conserved domain Combination.

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Conserved Domain C ombination In Protein Interaction

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  1. Conserved Domain CombinationIn Protein Interaction Jung, SukHoon October 16, 2009

  2. Contents • Background • Conserved Domain Combination • GO term evaluation • Evaluation on Primary DC for Protein Interaction • Discussion

  3. Conserved domain Combination • A set of protein domains that has been conserved through evolution • A cooperative team in order to realize the function • We proposed all-confidence as an index measuring the degree of conservation • We found that there are higher correlations between all-confidence and the functional similarity of domains than conventional support or confidence based approach

  4. GO term Evaluation • Gene Ontology term (GO term) describes the function of domains in three categories, molecular function, biological process, cellular component • GO term evaluation manifested that function of DC is more correlative with.. • all-confidence than that with support • Molecular function than biological process or cellular component • Conserved DC≒ Cooperative DC for molecular function Pearson’s correlation r= 0.464 Inner Functional Similarity Pearson’s correlation r= 0.205 All-confidence support All-confidence

  5. Evaluation on Primary Interacting DC (PIDC) • Protein-Protein Interaction (protein binding) is a type of molecular function. • PIDC ⊂ Cooperative DC for molecular function(Conserved DC) • For the actual example using 3D structures (337 cases) • All-confidence Significancy (AS) measures the relative significance (rank) of a DC in relation to other DCs in a protein • AS = 1, when the DC has highest all-confidence All-conf Significancy(dci)

  6. Evaluation on primary interacting DC • AS distinguishes PIDCs from others • Type 1 : PIDC (269) • Type 2 : subset of PIDC (139) • Type 3 : superset of PIDC (938) • Type 4 : random DC (5252) • Type 5 : non-PIDC (803) AS

  7. Evaluation on primary interacting DC • Further consideration • 2-member DCs tends to have a higher all-conf than that of 3- member DCs • PIDCs have two domains in 297 cases among 337 • In some protein, all domains participate in PIDC • so has no compared DCs • Some protein has multiple PIDC according to interaction partner • 307 proteins have PIDC in 337 cases • New type • Type 1 : PIDC • Type 2 : random DC • Type 3 : non-PIDC

  8. Evaluation 1 • 2-member PIDC • The number of cases: 269 -> 258 • # of type 1: 258 • # of type 2: 237 • # of type 3: 42 AS

  9. Evaluation 2 • After removal of proteins in which all domains participate in PIDC • The number of cases: 258 -> 83 • # of type 1: 83 • # of type 2: 237 • # of type 3: 42 AS

  10. Evaluation 3 • 30 Proteins use different PIDCs to interact with multiple partners. • In them, all PIDCs tend to have high AS, leading to confusion • The number of cases: 83-> 65 • # of type 1: 65 • # of type 2: 170 • # of type 3: 27 AS

  11. Issue • All-confidence + GO term evaluation + evaluation on PIDC can be reported in a paper • Further considerations weaken the evaluation on Primary Interacting DC for PPI • Decrease the number of cases to be investigated • Blur the functional significance of PIDC compared to other DCs

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