Publication

A foundational atlas of autism protein interactions reveals molecular convergence

Wang B, Vartak R, Zaltsman Y, Naing ZZC, Hennick KM, Polacco BJ, Bashir A, Eckhardt M, Bouhaddou M, Xu J, Sun N, Lasser M, Zhou Y, Guiley KZ, Chan U, Kaye JA, Khare P, Drake S, Drury V, Burke DF, Gonzalez S, Alkhairy S, Morris M, Baum T, Krasnoff R, Wang S, Pham P, Arbalaez J, Pratt D, Chag S, Rolland T, Bourgeron T, Finkbeiner S, Bandyopadhay S, Ideker T, Beltrao P, Willsey HR, Obernier K, Nowakowski TJ, Huttenhain R, State MW, Willsey AJ, Krogan NJ

Translating high-confidence (hc) autism spectrum disorder (ASD) genes into viable treatment targets remains elusive. We constructed a foundational protein-protein interaction (PPI) network in HEK293T cells involving 100 hcASD risk genes, revealing over 1,800 PPIs (87% novel). Interactors, expressed in the human brain and enriched for ASD but not schizophrenia genetic risk, converged on protein complexes involved in neurogenesis, tubulin biology, ... [more]

Quantitative Score

• 0.99037302 [compPASS Score]

Throughput

• High Throughput

Additional Notes

• APMS data generated in HEK293T by overexpression of Strep-tagged patient derived ASD variant. Intensity of the interaction between the WT protein and the hit protein was compared to the intensity of the interaction between the patient derived variant and hit protein. Significant interaction intensity changes were defined as those with a log2(fold-change) >= 1 and p <= 0.05. Strengthened interactions were denoted as 'Up', weakened interactions were denoted as 'Down' and unchanged interactions were denoted as 'Not significant' based on these scores. ASD variant: Bait protein name: C1095Y - Interaction Strength: not significant, Log2fc: 0.224338722830315, p-value: 0.0479485979863852
• APMS data generated in HEK293T by overexpression of Strep-tagged patient derived ASD variant. Intensity of the interaction between the WT protein and the hit protein was compared to the intensity of the interaction between the patient derived variant and hit protein. Significant interaction intensity changes were defined as those with a log2(fold-change) >= 1 and p <= 0.05. Strengthened interactions were denoted as 'Up', weakened interactions were denoted as 'Down' and unchanged interactions were denoted as 'Not significant' based on these scores. ASD variant: Bait protein name: L834P - Interaction Strength: not significant, Log2fc: 0.54115028719187, p-value: 0.0001846564948491
• APMS data generated in HEK293T by overexpression of Strep-tagged patient derived ASD variant. Intensity of the interaction between the WT protein and the hit protein was compared to the intensity of the interaction between the patient derived variant and hit protein. Significant interaction intensity changes were defined as those with a log2(fold-change) >= 1 and p <= 0.05. Strengthened interactions were denoted as 'Up', weakened interactions were denoted as 'Down' and unchanged interactions were denoted as 'Not significant' based on these scores. ASD variant: Bait protein name: M904I - Interaction Strength: not significant, Log2fc: 0.0751464533336695, p-value: 0.474897688039795
• APMS data generated in HEK293T by overexpression of Strep-tagged patient derived ASD variant. Intensity of the interaction between the WT protein and the hit protein was compared to the intensity of the interaction between the patient derived variant and hit protein. Significant interaction intensity changes were defined as those with a log2(fold-change) >= 1 and p <= 0.05. Strengthened interactions were denoted as 'Up', weakened interactions were denoted as 'Down' and unchanged interactions were denoted as 'Not significant' based on these scores. ASD variant: Bait protein name: Q696K - Interaction Strength: not significant, Log2fc: 0.0939127555095804, p-value: 0.374754835259382
• APMS data generated in HEK293T by overexpression of Strep-tagged patient derived ASD variant. Intensity of the interaction between the WT protein and the hit protein was compared to the intensity of the interaction between the patient derived variant and hit protein. Significant interaction intensity changes were defined as those with a log2(fold-change) >= 1 and p <= 0.05. Strengthened interactions were denoted as 'Up', weakened interactions were denoted as 'Down' and unchanged interactions were denoted as 'Not significant' based on these scores. ASD variant: Bait protein name: R1580W - Interaction Strength: not significant, Log2fc: 0.403723609411629, p-value: 0.0018828224186564
• Affinity purification-MS was used to capture high confidence wild-type protein interactors as defined by the thresholds: BFDR <= 0.05 and compPASS scores (rank_WD) >= 0.971. Baits are Strep-tagged proteins exogenously expressed in HEK 293T cells. ComPASS score: 0.99037302

Related interactions

Curated By

• BioGRID