Background: How to detect protein complexes is an important and challenging task in post genomic era. As the increasing amount of protein-protein interaction (PPI) data are available, we are able to identify protein complexes from PPI networks. However, most of current studies detect protein complexes based solely on the observation that dense regions in PPI networks may correspond to protein complexes, but fail to consider the inherent organization within protein complexes. Results: To provide insights into the organization of protein complexes, this paper presents a novel core-attachment based method (COACH) which detects protein complexes in two stages. It first detects protein-complex cores as the "hearts" of protein complexes and then includes attachments into these cores to form biologically meaningful structures. We evaluate and analyze our predicted protein complexes from two aspects. First, we perform a comprehensive comparison between our proposed method and existing techniques by comparing the predicted complexes against benchmark complexes. Second, we also validate the core-attachment structures using various biological evidence and knowledge. Conclusion: Our proposed COACH method has been applied on two different yeast PPI networks and the experimental results show that COACH performs significantly better than the state-of-the-art techniques. In addition, the identified complexes with core-attachment structures are demonstrated to match very well with existing biological knowledge and thus provide more insights for future biological study.

Most proteins form macromolecular complexes to perform their biological functions. However, experimentally determined protein complex data, especially of those involving more than two protein partners, are relatively limited in the current state-of-the-art high-throughput experimental techniques. Nevertheless, many techniques (such as yeast-two-hybrid) have enabled systematic screening of pairwise protein-protein interactions en masse. Thus computational approaches for detecting protein complexes from protein interaction data are useful complements to the limited experimental methods. They can be used together with the experimental methods for mapping the interactions of proteins to understand how different proteins are organized into higher-level substructures to perform various cellular functions.

Utilizing powerful Large Language Models (LLMs) for generative recommendation has attracted much attention. Nevertheless, a crucial challenge is transforming recommendation data into the language space of LLMs through effective item tokenization. Current approaches, such as ID, textual, and codebook-based identifiers, exhibit shortcomings in encoding semantic information, incorporating collaborative signals, or handling code assignment bias. To address these limitations, we propose LETTER (a LEarnable Tokenizer for generaTivE Recommendation), which integrates hierarchical semantics, collaborative signals, and code assignment diversity to satisfy the essential requirements of identifiers. LETTER incorporates Residual Quantized VAE for semantic regularization, a contrastive alignment loss for collaborative regularization, and a diversity loss to mitigate code assignment bias. We instantiate LETTER on two models and propose a ranking-guided generation loss to augment their ranking ability theoretically. Experiments on three datasets validate the superiority of LETTER, advancing the state-of-the-art in the field of LLM-based generative recommendation.

Motivation: Experimental limitations in high-throughput protein–protein interaction detection methods have resulted in low quality interaction datasets that contained sizable fractions of false positives and false negatives. Small-scale, focused experiments are then needed to complement the high-throughput methods to extract true protein interactions. However, the naturally vast interactomes would require much more scalable approaches. Results: We describe a novel method called IRAP^* as a computational complement for repurification of the highly erroneous experimentally derived protein interactomes. Our method involves an iterative process of removing interactions that are confidently identified as false positives and adding interactions detected as false negatives into the interactomes. Identification of both false positives and false negatives are performed in IRAP^* using interaction confidence measures based on network topological metrics. Potential false positives are identified amongst the detected interactions as those with very low computed confidence values, while potential false negatives are discovered as the undetected interactions with high computed confidence values. Our results from applying IRAP^* on large-scale interaction datasets generated by the popular yeast-two-hybrid assays for yeast, fruit fly and worm showed that the computationally repurified interaction datasets contained potentially lower fractions of false positive and false negative errors based on functional homogeneity. Availability: The confidence indices for PPIs in yeast, fruit fly and worm as computed by our method can be found at our website Contact:skng@i2r.a-star.edu.sg Supplementary information: Supplementary data are available at Bioinformatics online.

Harnessing Large Language Models (LLMs) for recommendation is rapidly emerging, which relies on two fundamental steps to bridge the recommendation item space and the language space: 1) item indexing utilizes identifiers to represent items in the language space, and 2) generation grounding associates LLMs' generated token sequences to in-corpus items. However, previous methods exhibit inherent limitations in the two steps. Existing ID-based identifiers (e.g., numeric IDs) and description-based identifiers (e.g., titles) either lose semantics or lack adequate distinctiveness. Moreover, prior generation grounding methods might generate invalid identifiers, thus misaligning with in-corpus items. To address these issues, we propose a novel Transition paradigm for LLM-based Recommender (named TransRec) to bridge items and language. Specifically, TransRec presents multi-facet identifiers, which simultaneously incorporate ID, title, and attribute for item indexing to pursue both distinctiveness and semantics. Additionally, we introduce a specialized data structure for TransRec to ensure generating valid identifiers only and utilize substring indexing to encourage LLMs to generate from any position of identifiers. Lastly, TransRec presents an aggregated grounding module to leverage generated multi-facet identifiers to rank in-corpus items efficiently. We instantiate TransRec on two backbone models, BART-large and LLaMA-7B.