Biomedical subjects

Lusheng Wang

Publications and source records attributed to Lusheng Wang.

10 recordsLinked to original sources

PubMed2026

Cell-type specific activation of the cGAS-STING pathway in tumor immunotherapy: mechanisms and therapeutic implications.

BACKGROUND: The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) pathway acts as a pivotal innate immune sensor that detects cytosolic DNA and links genomic instability to antitumor immune activation. Therapeutic activation of this pathway has garnered substantial interest as a strategy to enhance cancer immunotherapy by promoting dendritic cell maturation, augmenting antigen presentation, and facilitating cytotoxic lymphocyte infiltration. However, the functional outcomes of cGAS–STING signaling are highly context dependent and influenced by both cell type and tumor microenvironmental (TME) conditions. MAIN BODY: Recent advances in single-cell and spatial transcriptomic profiling have revealed profound heterogeneity in cGAS–STING activation across distinct cellular and regional compartments within tumors. Acute and spatially restricted activation of the pathway can elicit potent antitumor immune responses, whereas chronic or dysregulated signaling may promote immune tolerance and tumor progression. Moreover, metabolic stress, epigenetic silencing, and microenvironmental immunosuppressive factors such as TGF-β and IL-10 can further modulate STING activity, leading to resistance to immunotherapy. Current translational efforts focus on next-generation STING agonists, nanoparticle-based delivery systems, and rational combination strategies with immune checkpoint blockade and metabolic modulators to overcome tumor-intrinsic resistance and minimize systemic toxicity. CONCLUSIONS: Understanding the cell-type-specific and spatial dynamics of cGAS–STING signaling is crucial for the rational design of precision immunotherapies. Future research should emphasize context-dependent modulation of STING activity to maximize therapeutic benefit while limiting adverse effects. Integrating multi-omics technologies and spatially guided drug delivery may ultimately enable personalized modulation of the cGAS–STING axis, transforming it into a clinically effective and safe strategy for cancer immunotherapy.

Humans↗

PubMed2006

Finding the region of pseudo-periodic tandem repeats in biological sequences.

The genomes of many species are dominated by short sequences repeated consecutively. It is estimated that over 10% of the human genome consists of tandemly repeated sequences. Finding repeated regions in long sequences is important in sequence analysis. We develop a software, LocRepeat, that finds regions of pseudo-periodic repeats in a long sequence. We use the definition of Li et al. 1 for the pseudo-periodic partition of a region and extend the algorithm that can select the repeated region from a given long sequence and give the pseudo-periodic partition of the region.

Journal Article↗

PubMed2005

Community-based health insurance in poor rural China: the distribution of net benefits.

The collapse of China's Cooperative Medical System (CMS) in 1978 resulted in the lack of an organized financing scheme for health care, adversely affecting rural farmers' access to health care, especially among the poor. The Chinese government recently announced a policy to re-establish some forms of community-based insurance (CBI). Many existing schemes involve low premiums but high co-payments. We hypothesized that such benefit design leads to unequal distribution of the "net benefits" (NB)--benefits net of payment--because even though low premiums are more affordable to poor farmers, high co-payments may have a significant deterrent effect on the poor in the use of services in CBI. To test this hypothesis empirically, we estimated the probability of farmers joining a re-established CBI using logistic regression, and the utilization of health care services for those who joined the scheme using the two-part model. Based on the estimations, we predicted the distribution of NB among those who joined the CBI and for the entire population in the community. Our data came from a household survey of 4160 members of 1173 households conducted in six villages in Fengshan Township, Guizhou Province, China. Three principal findings emerged from this study. First, income is an important factor influencing farmers' decision to join a CBI despite the premium representing a very small fraction of household income. Secondly, both income and health status influence enrollees' utilization of health services: richer/sicker participants obtain greater NB from the CBI than poorer/healthier members, meaning that the poorer/healthier participants subsidize the rich/sick. Thirdly, wealthy farmers benefit the most from the CBI with low premium and high co-payment features at every level of health status. In conclusion, policy recommendations related to the improvement of the benefit distribution of CBI schemes are made based on the results from this study.

Adolescent↗

PubMed2005

Randomized algorithms for motif detection.

MOTIVATION: Motif detection for DNA sequences has many important applications in biological studies, e.g. locating binding sites regulatory signals, designing genetic probes etc. In this paper, we propose a randomized algorithm, design an improved EM algorithm and combine them to form a software tool. RESULTS: (1) We design a randomized algorithm for consensus pattern problem. We can show that with high probability, our randomized algorithm finds a pattern in polynomial time with cost error at most x l for each string, where l is the length of the motif and can be any positive number given by the user. (2) We design an improved EM algorithm that outperforms the original EM algorithm. (3) We develop a software tool, MotifDetector, that uses our randomized algorithm to find good seeds and uses the improved EM algorithm to do local search. We compare MotifDetector with Buhler and Tompa's PROJECTION which is considered to be the best known software for motif detection. Simulations show that MotifDetector is slower than PROJECTION when the pattern length is relatively small, and outperforms PROJECTION when the pattern length becomes large. AVAILABILITY: It is available for free at http://www.cs.cityu.edu.hk/~lwang/software/motif/index.html, subject to copyright restrictions.

Algorithms↗

PubMed2004

CTRD: a fast applet for computing signed translocation distance between genomes.

CTRD is a software for computing translocation distance between genomes. It takes two genomes as its input and tests whether one genome can be transformed into the other. If possible, it computes the translocation distance between two genomes, and gives the translocation operation serial. We adopt the fastest known O(n(2)log n) algorithm. Our contributions include (1) give a necessary and sufficient condition to ensure that one genome can be transformed into the other for translocation operations, and (2) develop a software using the fastest known O(n(2)log n) algorithm.

Algorithms↗

PubMed2003

Parametric alignment of ordered trees.

MOTIVATION: Computing the similarity between two ordered trees has applications in RNA secondary structure comparison, genetics and chemical structure analysis. Alignment of tree is one of the proposed measures. Similar to pair-wise sequence comparison, there is often disagreement about how to weight matches, mismatches, indels and gaps when we compare two trees. For sequence comparison, the parametric sequence alignment tools have been developed. The users are allowed to see explicitly and completely the effect of parameter choices on the optimal sequence alignments. A similar tool for aligning two ordered trees is required in practice. RESULTS: We develop a parametric tool for aligning two ordered trees that allow users to see the effect of parameter choices on the optimal alignment of trees. Our contributions include: (1) develop a parametric tool for aligning two ordered trees; (2) design an efficient algorithm for aligning two ordered trees with gap penalties that runs in O(n(2)deg(2)) time, where n is the number of nodes in the trees and deg is the degree of the trees; and (3) reduce the space of the algorithm from O(n(2)deg(2)) to O(n log n. deg(2)). AVAILABILITY: The software is available at http://www.cs.cityu.edu.hk/~lwang/software/ParaTree

Algorithms↗

PubMed2003

Haplotype inference by maximum parsimony.

MOTIVATION: Haplotypes have been attracting increasing attention because of their importance in analysis of many fine-scale molecular-genetics data. Since direct sequencing of haplotype via experimental methods is both time-consuming and expensive, haplotype inference methods that infer haplotypes based on genotype samples become attractive alternatives. RESULTS: (1) We design and implement an algorithm for an important computational model of haplotype inference that has been suggested before in several places. The model finds a set of minimum number of haplotypes that explains the genotype samples. (2) Strong supports of this computational model are given based on the computational results on both real data and simulation data. (3) We also did some comparative study to show the strength and weakness of this computational model using our program. AVAILABILITY: The software HAPAR is free for non-commercial uses. Available upon request (lwang@cs.cityu.edu.hk).

Algorithms↗

PubMed2003

Greedy method for inferring tandem duplication history.

MOTIVATION: Genome analysis suggests that tandem duplication is an important mode of evolutionary novelty by permitting one copy of each gene to drift and potentially to acquire a new function. With more and more genomic sequences available, reconstructing duplication history has received extensive attention recently. RESULTS: An efficient method is presented for inferring the duplication history of tandemly repeated sequences based on the model proposed by Fitch (1977). We validate the method by using simulation results and real data sets of mucin genes, ZNF genes, and olfactory receptors genes. The agreement with conclusions drawn by other biological researchers strongly indicates that our method is efficient and robust. AVAILABILITY: The program is available by request.

Algorithms↗

PubMed2003

SEGID: identifying interesting segments in (multiple) sequence alignments.

SUMMARY: SEGID is a tool for finding conserved regions (regions of high scores) for a given (multiple) sequence alignment. It takes a (multiple) sequence alignment as its input and converts the alignment into a sequence of numbers, where each number is the alignment score of a column. Three algorithms are used to identify regions of high scores. A graphical interface is provided to present those identified regions. AVAILABILITY: Free from http://www.cs.cityu.edu.hk/~lwang/segid/subject to copyright restrictions.

Algorithms↗

PubMed2003

The inverse problems for some topological indices in combinatorial chemistry.

In the original paper, Goldman et al. (2000) launched the study of the inverse problems in combinatorial chemistry, which is closely related to the design of combinatorial libraries for drug discovery. Following their ideas, we investigate four other topological indices, i.e., the sigma-index, the c-index, the Z-index, and the M(1)-index, with a special emphasis on the sigma-index. Like the Wiener index, these four indices are very popular in combinatorial chemistry and reflect many chemical and physical properties. We give algorithmic and analytical solutions for the inverse problems of the four indices. We also show that the SUBTREEVALUE reconstruction problem for the sigma-index is NP-hard.

Algorithms↗