Pro­teins make up the machinery of the cell. Their inter­ac­tion with each other is respon­sible for how the cell func­tions within a living organism. Intrigued by what these inter­ac­tions may look like, sci­en­tists have been working to map net­works of phys­ical DNA-​​, RNA-​​, and protein-​​protein inter­ac­tions. North­eastern Uni­ver­sity physi­cist Albert-​​László Barabási, in col­lab­o­ra­tion with a research team lead by Marc Vidal from Dana Farber Cancer Insti­tute, car­ried out a com­par­a­tive quality assess­ment of binary inter­ac­tions using the yeast S. cere­visiae as a model system.

In order to better under­stand inter­ac­tome net­work struc­ture and func­tions, Barabási and his col­lab­o­ra­tors devel­oped advanced method­ology to ana­lyze cur­rently avail­able maps by com­paring the quality of existing high-​​throughput binary and co-​​complex data sets to infor­ma­tion obtained from curating low-​​throughput experiments.

In the paper dis­cussing the study, the authors talk about exten­sive quality assess­ments, during which they found that pro­tein con­nec­tivity within cells sig­nif­i­cantly influ­ences the phe­no­type of the cells. In iden­ti­fying sev­eral hun­dreds of inter­ac­tions between high-​​quality binary pro­teins and testing and re-​​testing those to filter out false pos­i­tives, the group devel­oped an empir­i­cally con­trolled map­ping frame­work to pro­duce a second-​​generation high-​​quality, high-​​throughput Y2H data set cov­ering 20% of all yeast binary interactions.

While relying on con­firmed protein-​​protein inter­ac­tions beyond those seen in pre­vious studies, this study con­firmed that the more con­nected pro­teins are, the more con­se­quen­tial their actions will be for the behavior and the phe­no­type of the entire cell. The high-​​quality inter­ac­tion map and the research team cre­ated as a result of this col­lab­o­ra­tion will take under­standing of the inter­ac­tome network’s global and local prop­er­ties and its rela­tion­ship with mul­ti­cel­lular func­tions to a new level.

We found that only a few per­cent of the newly iden­ti­fied inter­ac­tions are false-​​positives, which is much lower than pre­vious quality assess­ments of large-​​scale yeast two-​​hybrid exper­i­ments sug­gested,” said Barabási, Dis­tin­guished Pro­fessor of Physics and Director of the Center for Com­plex Net­workRe­search at North­eastern Uni­ver­sity. “We can con­clude that pro­tein con­nec­tivity cor­re­lates with genetic pleiotropy, i.e. the more con­nected is a pro­tein, the larger the con­se­quences of its removal.”

The study, con­ducted in col­lab­o­ra­tion with Boston’s Dana Farber Cancer Insti­tute and Har­vard Med­ical School, appeared in the latest issue of Sci­ence magazine.

For more infor­ma­tion, please con­tact Renata Nyul at 617–373-7424 or at r.​nyul@​neu.​edu.

About North­eastern

Founded in 1898, North­eastern Uni­ver­sity is a pri­vate research uni­ver­sity located in the heart of Boston. North­eastern is a leader in inter­dis­ci­pli­nary research, urban engage­ment, and the inte­gra­tion of class­room learning with real-​​world expe­ri­ence. The university’s dis­tinc­tive coop­er­a­tive edu­ca­tion pro­gram, where stu­dents alter­nate semes­ters of full-​​time study with semes­ters of paid work in fields rel­e­vant to their pro­fes­sional inter­ests and major, is one of the largest and most inno­v­a­tive in the world. The Uni­ver­sity offers a com­pre­hen­sive range of under­grad­uate and grad­uate pro­grams leading to degrees through the doc­torate in six under­grad­uate col­leges, eight grad­uate schools, and two part-​​time divi­sions. For more infor­ma­tion, please visit www​.north​eastern​.edu.