A Bayesian networks approach for predicting protein-protein interactions from genomic data

We have developed an approach using Bayesian networks to predict protein-protein interactions genome-wide in yeast. Our method naturally weights and combines into reliable predictions genomic features only weakly associated with interaction (e.g., messenger RNAcoexpression, coessentiality, and colocalization). In addition to de novo predictions, it can integrate often noisy, experimental interaction data sets. We observe that at given levels of sensitivity, our predictions are more accurate than the existing high-throughput experimental data sets. We validate our predictions with TAP (tandem affinity purification) tagging experiments. Our analysis, which gives a comprehensive view of yeast interactions, is available at genecensus.org/intint.     

孔石莼和赤潮异弯藻相互作用的初步研究

选用大型海藻——孔石莼Ulva pertusa和赤潮微藻——赤潮异弯藻Heterosigma akashiwo为试验材料,在实验室条件下研究了藻体、培养液滤液和胞内物质对生长相互作用的影响。结果表明:孔石莼和赤潮异弯藻二者之间存在克生效应,孔石莼培养液滤液和胞内物质对赤潮异弯藻生长有显著的抑制作用(P<0.01),而赤潮异弯藻培养液滤液和胞内物质对孔石莼生长亦有显著的抑制作用(P<0.01)。可以推测:孔石莼可能是通过分泌次生物质来抑制赤潮异弯藻的生长,而赤潮异弯藻可能是通过细胞的直接接触和分泌次生物质完成对孔石莼生长的抑制,其抑制物均存在于藻体和培养液中。     

孔石莼和赤潮异弯藻相互作用的初步研究

选用大型海藻——孔石莼Ulvapertusa和赤潮微藻——赤潮异弯藻Heterosigmaakashiwo为试验材料,在实验室条件下研究了藻体、培养液滤液和胞内物质对生长相互作用的影响。结果表明：孔石莼和赤潮异弯藻二者之间存在克生效应,孔石莼培养液滤液和胞内物质对赤潮异弯藻生长有显著的抑制作用（P〈0．01）,而赤潮异弯藻培养液滤液和胞内物质对孔石莼生长亦有显著的抑制作用（P〈O．01）。可以推测：孔石莼可能是通过分泌次生物质来抑制赤潮异弯藻的生长,而赤潮异弯藻可能是通过细胞的直接接触和分泌次生物质完成对孔石莼生长的抑制,其抑制物均存在于藻体和培养液中。     

Screening for nitric oxide-dependent protein-protein interactions

Because nitric oxide (NO) may be a ubiquitous regulator of cellular signaling, we have modified the yeast two-hybrid system to explore the possibility of NO-dependent protein-protein interactions. We screened for binding partners of procaspase-3, a protein implicated in apoptotic signaling pathways, and identified multiple NO-dependent interactions.Two such interactions, with acid sphingomyelinase and NO synthase, were shown to occur in mammalian cells dependent on endogenous NO. Nitrosylation may thus provide a broad-based mechanism for regulating interactions between proteins. If so, systematic proteomic analyses in which redox state and NO bioavailability are carefully controlled will reveal a large array of novel interactions.     

Designing small-molecule switches for protein-protein interactions

Mutations introduced into human growth hormone (hGH) (Thr175 --> Gly-hGH) and the extracellular domain of the hGH receptor (Trp104 --> Gly-hGHbp) created a cavity at the protein-protein interface that resulted in binding affinity being reduced by a factor of 10(6). A small library of indole analogs was screened for small molecules that bind the cavity created by the mutations and restore binding affinity. The ligand 5-chloro-2-trichloromethylimidazole was found to increase the affinity of the mutant hormone for its receptor more than 1000-fold. Cell proliferation and JAK2 phosphorylation assays showed that the mutant hGH activates growth hormone signaling in the presence of added ligand. This approach may allow other protein-protein and protein-nucleic acid interactions to be switched on or off by the addition or depletion of exogenous small molecules.     

Local interactions select for lower pathogen infectivity

Theory suggests that the current rapid increase in connectivity and consequential changes in the structure of human, agricultural, and wildlife populations may select for parasite strains with higher infectivity. We carried out a test of this spatial theory by experimentally altering individual host movement rates in a model host/pathogen system by altering the viscosity of their environment. In our microevolutionary selection experiments, the infectivity of the virus was, as predicted by the theory, reduced in the most viscous populations. We therefore provide empirical support for the theory that population structure affects the evolution of infectious organisms.     

Pseudomonas-Candida interactions: an ecological role for virulence factors

Bacterial-fungal interactions have great environmental, medical, and economic importance, yet few have been well characterized at the molecular level. Here, we describe a pathogenic interaction between Pseudomonas aeruginosa and Candida albicans, two opportunistic pathogens. P. aeruginosa forms a dense biofilm on C. albicans filaments and kills the fungus. In contrast, P. aeruginosa neither binds to nor kills yeast-form C. albicans. Several P. aeruginosa virulence factors that are important in disease are involved in the killing of C. albicans filaments. We propose that many virulence factors studied in the context of human infection may also have a role in bacterial-fungal interactions.     

细菌根际黏附的界面作用机制研究

界面作用是细菌在环境中黏附、定殖、形成生物膜和发挥生态功能的基础和前提,对植物吸收养分、病原微生物拮抗具有重要意义。微生物-植物根际相互作用研究大多数从生态学和分子生物学角度出发,应用多种组学手段研究根系分泌物对于根际微生物定殖数量、群落组成和生理功能的影响,忽略了细菌定殖过程中物理、化学的界面作用机制及其对黏附的贡献。本文从界面作用机制出发,探讨了不同类型根系分泌物对细菌表面性质、细菌胞外聚合物（EPS）分子组成以及黏附功能的调控作用;梳理了黏附过程中细菌-植物生物大分子相互作用的主要模式及其微观机制;归纳了根际定殖过程可视化研究方法和微生物-植物生物大分子相互作用的分析手段;提出了根际生物分子组成分析、黏附蛋白质功能预测、根际定殖原位观测方法等亟需加强的研究方向。     

Interferon induction: tool for establishing interactions among homopolyribonucleotides

Hitherto unrecognized interactions between homopolyribonucleotides and complexes thereof are suggested by interferon induction data obtained in a highly sensitive assay system of primary rabbit kidney cell cultures superinduced by metabolic inhibitors.