The STRING database in 2025: protein networks with directionality of regulation

Abstract

Proteins cooperate, regulate and bind each other to achieve their functions. Understanding the complex network of their interactions is essential for a systems-level description of cellular processes. The STRING database compiles, scores and integrates protein-protein association information drawn from experimental assays, computational predictions and prior knowledge. Its goal is to create comprehensive and objective global networks that encompass both physical and functional interactions. Additionally, STRING provides supplementary tools such as network clustering and pathway enrichment analysis. The latest version, STRING 12.5, introduces a new 'regulatory network', for which it gathers evidence on the type and directionality of interactions using curated pathway databases and a fine-tuned language model parsing the literature. This update enables users to visualize and access three distinct network types-functional, physical and regulatory-separately, each applicable to distinct research needs. In addition, the pathway enrichment detection functionality has been updated, with better false discovery rate corrections, redundancy filtering and improved visual displays. The resource now also offers improved annotations of clustered networks and provides users with downloadable network embeddings, which facilitate the use of STRING networks in machine learning and allow cross-species transfer of protein information. The STRING database is available online at https://string-db.org/.

Graphical Abstract

Figure 1.

Illustration of the new ‘regulatory network’ mode in STRING, where the network edges visually indicate the direction, confidence and sources of each regulatory interaction. Clicking on an edge within the network brings up a pop-up window with a detailed overview of the available evidence and the annotated type of regulation. Users can further explore the data behind the interactions by accessing the specific evidence viewers linked within the pop-up, including the text-mining evidence viewer. This viewer presents excerpts from literature pertaining to the inspected interactions, as well as an automatically generated large language model summary of the presented excerpts.

Figure 2.

Enrichment analysis interface from the STRING database website. Left: Schematic of the enrichment analysis tab highlighting various sections of the webpage. Top right: A zoomed-in view of the analysis table with two user-highlighted terms (colored lines). Bottom right: A visualization of the enrichment depicting the two terms highlighted in corresponding colors.