Disentangling the Complex Multiplexed DIA Spectra in De Novo Peptide Sequencing

Data-Independent Acquisition (DIA) was introduced to improve sensitivity to cover all peptides in a range rather than only sampling high-intensity peaks as in Data-Dependent Acquisition (DDA) mass spectrometry. However, it is not very clear how useful DIA data is for de novo peptide sequencing as the DIA data are marred with coeluted peptides, high noises, and varying data quality. We present a new deep learning method DIANovo, and address each of these difficulties, and improves the previous established system DeepNovo-DIA by from 25% to 81%, averaging 48%, for amino acid recall, and by from 27% to 89%, averaging 57%, for peptide recall, by equipping the model with a deeper understanding of coeluted DIA spectra. This paper also provides criteria about when DIA data could be used for de novo peptide sequencing and when not to by providing a comparison between DDA and DIA, in both de novo and database search mode. We find that while DIA excels with narrow isolation windows on older-generation instruments, it loses its advantage with wider windows. However, with Orbitrap Astral, DIA consistently outperforms DDA due to narrow window mode enabled. We also provide a theoretical explanation of this phenomenon, emphasizing the critical role of the signal-to-noise profile in the successful application of de novo sequencing.

Towards Cross-domain Few-shot Graph Anomaly Detection

Few-shot graph anomaly detection (GAD) has recently garnered increasing attention, which aims to discern anomalous patterns among abundant unlabeled test nodes under the guidance of a limited number of labeled training nodes. Existing few-shot GAD approaches typically adopt meta-training methods trained on richly labeled auxiliary networks to facilitate rapid adaptation to target networks that possess sparse labels. However, these proposed methods often assume that the auxiliary and target networks exist in the same data distributions-an assumption rarely holds in practical settings. This paper explores a more prevalent and complex scenario of cross-domain few-shot GAD, where the goal is to identify anomalies within sparsely labeled target graphs using auxiliary graphs from a related, yet distinct domain. The challenge here is nontrivial owing to inherent data distribution discrepancies between the source and target domains, compounded by the uncertainties of sparse labeling in the target domain. In this paper, we propose a simple and effective framework, termed CDFS-GAD, specifically designed to tackle the aforementioned challenges. CDFS-GAD first introduces a domain-adaptive graph contrastive learning module, which is aimed at enhancing cross-domain feature alignment. Then, a prompt tuning module is further designed to extract domain-specific features tailored to each domain. Moreover, a domain-adaptive hypersphere classification loss is proposed to enhance the discrimination between normal and anomalous instances under minimal supervision, utilizing domain-sensitive norms. Lastly, a self-training strategy is introduced to further refine the predicted scores, enhancing its reliability in few-shot settings. Extensive experiments on twelve real-world cross-domain data pairs demonstrate the effectiveness of the proposed CDFS-GAD framework in comparison to various existing GAD methods.