We introduce a new graph diffusion model for small drug molecule generation which simultaneously offers a 10-fold reduction in the number of diffusion steps when compared to existing methods, preservation of small molecule graph motifs via motif compression, and an average 3\% improvement in SMILES validity over the DiGress model across all real-world molecule benchmarking datasets. Furthermore, our approach outperforms the state-of-the-art DeFoG method with respect to motif-conservation by roughly 4\%, as evidenced by high ChEMBL-likeness, QED and newly introduced shingles distance scores. The key ideas behind the approach are to use a combination of deterministic and random subgraph perturbations, so that the node and edge noise schedules are codependent; to modify the loss function of the training process in order to exploit the deterministic component of the schedule; and, to ''compress'' a collection of highly relevant carbon ring and other motif structures into supernodes in a way that allows for simple subsequent integration into the molecular scaffold.

BACKGROUND: Pathogenic infections pose a significant threat to global health, affecting millions of people every year and presenting substantial challenges to healthcare systems worldwide. Efficient and timely testing plays a critical role in disease control and transmission prevention. Group testing is a well-established method for reducing the number of tests needed to screen large populations when the disease prevalence is low. However, it does not fully utilize the quantitative information provided by qPCR methods, nor is it able to accommodate a wide range of pathogen loads. RESULTS: To address these issues, we introduce a novel adaptive semi-quantitative group testing (SQGT) scheme to efficiently screen populations via two-stage qPCR testing. The SQGT method quantizes cycle threshold (Ct) values into multiple bins, leveraging the information from the first stage of screening to improve the detection sensitivity. Dynamic Ct threshold adjustments mitigate dilution effects and enhance test accuracy. Comparisons with traditional binary outcome GT methods show that SQGT reduces the number of tests by 24% on the only complete real-world qPCR group testing dataset from Israel, while maintaining a negligible false negative rate. CONCLUSION: In conclusion, our adaptive SQGT approach, utilizing qPCR data and dynamic threshold adjustments, offers a promising solution for efficient population screening. With a reduction in the number of tests and minimal false negatives, SQGT holds potential to enhance disease control and testing strategies on a global scale.

Dictionary learning (DL), implemented via matrix factorization (MF), is commonly used in computational biology to tackle ubiquitous clustering problems. The method is favored due to its conceptual simplicity and relatively low computational complexity. However, DL algorithms produce results that lack interpretability in terms of real biological data. Additionally, they are not optimized for graph-structured data and hence often fail to handle them in a scalable manner. In order to address these limitations, we propose a novel DL algorithm called online convex network dictionary learning (online cvxNDL). Unlike classical DL algorithms, online cvxNDL is implemented via MF and designed to handle extremely large datasets by virtue of its online nature. Importantly, it enables the interpretation of dictionary elements, which serve as cluster representatives, through convex combinations of real measurements. Moreover, the algorithm can be applied to data with a network structure by incorporating specialized subnetwork sampling techniques. To demonstrate the utility of our approach, we apply cvxNDL on 3D-genome RNAPII ChIA-Drop data with the goal of identifying important long-range interaction patterns (long-range dictionary elements). ChIA-Drop probes higher-order interactions, and produces data in the form of hypergraphs whose nodes represent genomic fragments. The hyperedges represent observed physical contacts. Our hypergraph model analysis has the objective of creating an interpretable dictionary of long-range interaction patterns that accurately represent global chromatin physical contact maps. Through the use of dictionary information, one can also associate the contact maps with RNA transcripts and infer cellular functions. To accomplish the task at hand, we focus on RNAPII-enriched ChIA-Drop data from Drosophila Melanogaster S2 cell lines. Our results offer two key insights. First, we demonstrate that online cvxNDL retains the accuracy of classical DL (MF) methods while simultaneously ensuring unique interpretability and scalability. Second, we identify distinct collections of proximal and distal interaction patterns involving chromatin elements shared by related processes across different chromosomes, as well as patterns unique to specific chromosomes. To associate the dictionary elements with biological properties of the corresponding chromatin regions, we employ Gene Ontology (GO) enrichment analysis and perform multiple RNA coexpression studies.

We consider the problem of determining the mutational support and distribution of the SARS-CoV-2 viral genome in the small-sample regime. The mutational support refers to the unknown number of sites that may eventually mutate in the SARS-CoV-2 genome while mutational distribution refers to the distribution of point mutations in the viral genome across a population. The mutational support may be used to assess the virulence of the virus and guide primer selection for real-time RT-PCR testing. Estimating the distribution of mutations in the genome of different subpopulations while accounting for the unseen may also aid in discovering new variants. To estimate the mutational support in the small-sample regime, we use GISAID sequencing data and our state-of-the-art polynomial estimation techniques based on new weighted and regularized Chebyshev approximation methods. For distribution estimation, we adapt the well-known Good-Turing estimator. Our analysis reveals several findings: First, the mutational supports exhibit significant differences in the ORF6 and ORF7a regions (older versus younger patients), ORF1b and ORF10 regions (females versus males) and in almost all ORFs (Asia/Europe/North America). Second, even though the N region of SARS-CoV-2 has a predicted 10% mutational support, mutations fall outside of the primer regions recommended by the CDC.

This letter presents an analysis of the queuing performance of a multiple-antenna cognitive radio system employing downlink beamforming. The paradigm of multiantenna zero-forcing beamforming is employed to null the interference at the primary users. A closed-form expression is derived for the probability density of successful packet transmission time followed by results for the average waiting and transmission times in an M/G/1 secondary user queuing system. Furthermore, this framework and the results are also extended to scenarios with ARQ and partial channel state information at the secondary transmitter. Numerical simulation results are presented to validate the theoretical performance analysis.