Plant Cell Environ. 2023 Jun 28. doi: 10.1111/pce.14647. Online ahead of print.

ABSTRACT

Viroids are circular RNAs of minimal complexity compelled to subvert plant-regulatory networks to accomplish their infectious process. Studies focused on the response to viroid-infection have mostly addressed specific regulatory levels and considered specifics infection-times. Thus, much remains to be done to understand the temporal evolution and complex nature of viroid-host interactions. Here we present an integrative analysis of the temporal evolution of the genome-wide alterations in cucumber plants infected with hop stunt viroid (HSVd) by integrating differential host transcriptome, sRNAnome and methylome. Our results support that HSVd promotes the redesign of the cucumber regulatory-pathways predominantly affecting specific regulatory layers at different infection-phases. The initial response was characterised by a reconfiguration of the host-transcriptome by differential exon-usage, followed by a progressive transcriptional downregulation modulated by epigenetic changes. Regarding endogenous small RNAs, the alterations were limited and mainly occurred at the late stage. Significant host-alterations were predominantly related to the downregulation of transcripts involved in plant-defence mechanisms, the restriction of pathogen-movement and the systemic spreading of defence signals. We expect that these data constituting the first comprehensive temporal-map of the plant-regulatory alterations associated with HSVd infection could contribute to elucidate the molecular basis of the yet poorly known host-response to viroid-induced pathogenesis.

PMID:37378473 | DOI:10.1111/pce.14647

iScience. 2023 May 25;26(6):106961. doi: 10.1016/j.isci.2023.106961. eCollection 2023 Jun 16.

ABSTRACT

A certain degree of uncertainty is always associated with the transcript abundance estimates. The uncertainty may make many downstream analyses, such as differential testing, difficult for certain transcripts. Conversely, gene-level analysis, though less ambiguous, is often too coarse-grained. We introduce TreeTerminus, a data-driven approach for grouping transcripts into a tree structure where leaves represent individual transcripts and internal nodes represent an aggregation of a transcript set. TreeTerminus constructs trees such that, on average, the inferential uncertainty decreases as we ascend the tree topology. The tree provides the flexibility to analyze data at nodes that are at different levels of resolution in the tree and can be tuned depending on the analysis of interest. We evaluated TreeTerminus on two simulated and two experimental datasets and observed an improved performance compared to transcripts (leaves) and other methods under several different metrics.

PMID:37378336 | PMC:PMC10291472 | DOI:10.1016/j.isci.2023.106961

iScience. 2023 May 28;26(6):106979. doi: 10.1016/j.isci.2023.106979. eCollection 2023 Jun 16.

ABSTRACT

In this study, we evaluated the effect of a specific synbiotic on CAC (AOM/DSS-induced colitis-associated cancer). We confirmed that the synbiotic intervention was able to protect the intestinal barrier and inhibit CAC occurrence via upregulating tight junction proteins and anti-inflammatory cytokines, and downregulating pro-inflammatory cytokines. Moreover, the synbiotic significantly improved the disorder of the colonic microbiota of CAC mice, promoted the formation of SCFAs and the production of secondary bile acids, and alleviated the accumulation of primary bile acids in the CAC mice. Meanwhile, the synbiotic could significantly inhibit the abnormal activation of the intestinal Wnt/β-catenin signaling pathway significantly related to IL-23. In a word, the synbiotic can inhibit the occurrence and development of colorectal tumors and it may be a functional food to prevent inflammation-related colon tumors, and the research also provided a theoretical basis for improving the intestinal microecological environment through diet therapy.

PMID:37378327 | PMC:PMC10291512 | DOI:10.1016/j.isci.2023.106979

iScience. 2023 May 28;26(6):106983. doi: 10.1016/j.isci.2023.106983. eCollection 2023 Jun 16.

ABSTRACT

Lineage plasticity, especially transdifferentiation between neural/neuroendocrine (NE) and non-NE lineage, has been observed in multiple cancer types and linked to increased tumor aggressiveness. However, existing NE/non-NE subtype classifications in various cancer types were established through ad hoc approaches in different studies, making it difficult to align findings across cancer types and extend investigations to new datasets. To address this issue, we developed a generalized strategy to generate quantitative NE scores and a web application to facilitate its implementation. We applied this method to nine datasets covering seven cancer types, including two neural cancers, two neuroendocrine cancers, and three non-NE cancers. Our analysis revealed significant NE inter-tumoral heterogeneity and identified strong associations between NE scores and molecular, histological, and clinical features, including prognosis in different cancer types. These results support the translational utility of NE scores. Overall, our work demonstrated a broadly applicable strategy for determining the NE properties of tumors.

PMID:37378310 | PMC:PMC10291506 | DOI:10.1016/j.isci.2023.106983

Front Oncol. 2023 Jun 12;13:1117810. doi: 10.3389/fonc.2023.1117810. eCollection 2023.

ABSTRACT

INTRODUCTION: Glucose and glutamine are major carbon and energy sources that promote the rapid proliferation of cancer cells. Metabolic shifts observed on cell lines or mouse models may not reflect the general metabolic shifts in real human cancer tissue.

METHOD: In this study, we conducted a computational characterization of the flux distribution and variations of the central energy metabolism and key branches in a pan-cancer analysis, including the glycolytic pathway, production of lactate, tricarboxylic acid (TCA) cycle, nucleic acid synthesis, glutaminolysis, glutamate, glutamine, and glutathione metabolism, and amino acid synthesis, in 11 cancer subtypes and nine matched adjacent normal tissue types using TCGA transcriptomics data.

RESULT: Our analysis confirms the increased influx in glucose uptake and glycolysis and decreased upper part of the TCA cycle, i.e., the Warburg effect, in almost all the analyzed cancer. However, increased lactate production and the second half of the TCA cycle were only seen in certain cancer types. More interestingly, we failed to detect significantly altered glutaminolysis in cancer tissues compared to their adjacent normal tissues. A systems biology model of metabolic shifts through cancer and tissue types is further developed and analyzed. We observed that (1) normal tissues have distinct metabolic phenotypes; (2) cancer types have drastically different metabolic shifts compared to their adjacent normal controls; and (3) the different shifts in tissue-specific metabolic phenotypes result in a converged metabolic phenotype through cancer types and cancer progression.

DISCUSSION: This study strongly suggests the possibility of having a unified framework for studies of cancer-inducing stressors, adaptive metabolic reprogramming, and cancerous behaviors.

PMID:37377905 | PMC:PMC10291142 | DOI:10.3389/fonc.2023.1117810

Cancer Cytopathol. 2023 Jun 28. doi: 10.1002/cncy.22732. Online ahead of print.

ABSTRACT

BACKGROUND: Adopting a computational approach for the assessment of urine cytology specimens has the potential to improve the efficiency, accuracy, and reliability of bladder cancer screening, which has heretofore relied on semisubjective manual assessment methods. As rigorous, quantitative criteria and guidelines have been introduced for improving screening practices (e.g., The Paris System for Reporting Urinary Cytology), algorithms to emulate semiautonomous diagnostic decision-making have lagged behind, in part because of the complex and nuanced nature of urine cytology reporting.

METHODS: In this study, the authors report on the development and large-scale validation of a deep-learning tool, AutoParis-X, which can facilitate rapid, semiautonomous examination of urine cytology specimens.

RESULTS: The results of this large-scale, retrospective validation study indicate that AutoParis-X can accurately determine urothelial cell atypia and aggregate a wide variety of cell-related and cluster-related information across a slide to yield an atypia burden score, which correlates closely with overall specimen atypia and is predictive of Paris system diagnostic categories. Importantly, this approach accounts for challenges associated with the assessment of overlapping cell cluster borders, which improve the ability to predict specimen atypia and accurately estimate the nuclear-to-cytoplasm ratio for cells in these clusters.

CONCLUSIONS: The authors developed a publicly available, open-source, interactive web application that features a simple, easy-to-use display for examining urine cytology whole-slide images and determining the level of atypia in specific cells, flagging the most abnormal cells for pathologist review. The accuracy of AutoParis-X (and other semiautomated digital pathology systems) indicates that these technologies are approaching clinical readiness and necessitates full evaluation of these algorithms in head-to-head clinical trials.

PMID:37377320 | DOI:10.1002/cncy.22732

J Exp Zool B Mol Dev Evol. 2023 Jun 28. doi: 10.1002/jez.b.23215. Online ahead of print.

NO ABSTRACT

PMID:37376917 | DOI:10.1002/jez.b.23215

Viruses. 2023 Jun 13;15(6):1363. doi: 10.3390/v15061363.

ABSTRACT

There is a significant overlap between HIV infection and substance-use disorders. Dopamine (DA) is the most abundantly upregulated neurotransmitter in methamphetamine abuse, with receptors (DRD1-5) that are expressed by neurons as well as by a large diversity of cell types, including innate immune cells that are the targets of HIV infection, making them responsive to the hyperdopaminergic environment that is characteristic of stimulant drugs. Therefore, the presence of high levels of dopamine may affect the pathogenesis of HIV, particularly in the brain. The stimulation of HIV latently infected U1 promonocytes with DA significantly increased viral p24 levels in the supernatant at 24 h, suggesting effects on activation and replication. Using selective agonists to different DRDs, we found that DRD1 played a major role in activating viral transcription, followed by DRD4, which increased p24 with a slower kinetic rate compared to DRD1. Transcriptome and systems biology analyses led to the identification of a cluster of genes responsive to DA, where S100A8 and S100A9 were most significantly correlated with the early increase in p24 levels following DA stimulation. Conversely, DA increased the expression of these genes' transcripts at the protein level, MRP8 and MRP14, respectively, which form a complex also known as calprotectin. Interestingly, MRP8/14 was able to stimulate HIV transcription in latent U1 cells, and this occurred via binding of the complex to the receptor for an advanced glycosylation end-product (RAGE). Using selective agonists, both DRD1 and DRD4 increased MRP8/14 on the surface, in the cytoplasm, as well as secreted in the supernatants. On the other hand, while DRD1/5 did not affect the expression of RAGE, DRD4 stimulation caused its downregulation, offering a mechanism for the delayed effect via DRD4 on the p24 increase. To cross-validate MRP8/14 as a DA signature with a biomarker value, we tested its expression in HIV+ Meth users' postmortem brain specimens and peripheral cells. MRP8/14+ cells were more frequently identified in mesolimbic areas such as the basal ganglia of HIV+ Meth+ cases compared to HIV+ non-Meth users or to controls. Likewise, MRP8/14+ CD11b+ monocytes were more frequent in HIV+ Meth users, particularly in specimens from participants with a detectable viral load in the CSF. Overall, our results suggest that the MRP8 and MRP14 complex may serve as a signature to distinguish subjects using addictive substances in the context of HIV, and that this may play a role in aggravating HIV pathology by promoting viral replication in people with HIV who use Meth.

PMID:37376663 | DOI:10.3390/v15061363

Polymers (Basel). 2023 Jun 8;15(12):2607. doi: 10.3390/polym15122607.

ABSTRACT

We propose and demonstrate dendrimer-based coatings for a sensitive biochip surface that enhance the high-performance sorption of small molecules (i.e., biomolecules with low molecular weights) and the sensitivity of a label-free, real-time photonic crystal surface mode (PC SM) biosensor. Biomolecule sorption is detected by measuring changes in the parameters of optical modes on the surface of a photonic crystal (PC). We describe the step-by-step biochip fabrication process. Using oligonucleotides as small molecules and PC SM visualization in a microfluidic mode, we show that the PAMAM (poly-amidoamine)-modified chip's sorption efficiency is almost 14 times higher than that of the planar aminosilane layer and 5 times higher than the 3D epoxy-dextran matrix. The results obtained demonstrate a promising direction for further development of the dendrimer-based PC SM sensor method as an advanced label-free microfluidic tool for detecting biomolecule interactions. Current label-free methods for small biomolecule detection, such as surface plasmon resonance (SPR), have a detection limit down to pM. In this work, we achieved for a PC SM biosensor a Limit of Quantitation of up to 70 fM, which is comparable with the best label-using methods without their inherent disadvantages, such as changes in molecular activity caused by labeling.

PMID:37376252 | DOI:10.3390/polym15122607

Pharmaceutics. 2023 Jun 20;15(6):1777. doi: 10.3390/pharmaceutics15061777.

ABSTRACT

β-defensins are one of the most abundant and studied families of antimicrobial peptides (AMPs). Because of their selective toxicity to bacterial membranes and a broad spectrum of microbicidal action, β-defensins are regarded as potential therapeutic agents. This work focuses on a β-defensin-like AMP from the spiny lobster Panulirus argus (hereafter referred to as panusin or PaD). This AMP is structurally related to mammalian defensins via the presence of an αβ domain stabilized by disulfide bonds. Previous studies of PaD suggest that its C-terminus (Ct_PaD) contains the main structural determinants of antibacterial activity. To confirm this hypothesis, we made synthetic versions of PaD and Ct_PaD to determine the influence of the C-terminus on antimicrobial activity, cytotoxicity, proteolytic stability, and 3D structure. After successful solid-phase synthesis and folding, antibacterial assays of both peptides showed truncated Ct_PaD to be more active than native PaD, confirming the role of the C-terminus in activity and suggesting that cationic residues in that region enhance binding to negatively charged membranes. On the other hand, neither PaD nor Ct_PaD were hemolytic or cytotoxic in human cells. Proteolysis in human serum was also studied, showing high (>24 h) t1/2 values for PaD and lower but still considerable for Ct_PaD, indicating that the missing native disulfide bond in Ct_PaD alters protease resistance, albeit not decisively. NMR-2D experiments in water agree with the results obtained by circular dichroism (CD), where in SDS micelles, CD showed both peptides adopting an increasingly ordered structure in a hydrophobic environment, in tune with their ability to perturb bacterial membrane systems. In conclusion, while the β-defensin features of PaD are confirmed as advantageous in terms of antimicrobial activity, toxicity, and protease stability, the results of the present work suggest that these same features are preserved, even enhanced, in the structurally simpler Ct_PaD, which must therefore be viewed as a valuable lead for the development of novel anti-infectives.

PMID:37376223 | DOI:10.3390/pharmaceutics15061777

Plants (Basel). 2023 Jun 19;12(12):2367. doi: 10.3390/plants12122367.

ABSTRACT

Soil salinity can impose substantial stress on plant growth and cause significant yield losses. Crop varieties tolerant to salinity stress are needed to sustain yields in saline soils. This requires effective genotyping and phenotyping of germplasm pools to identify novel genes and QTL conferring salt tolerance that can be utilised in crop breeding schemes. We investigated a globally diverse collection of 580 wheat accessions for their growth response to salinity using automated digital phenotyping performed under controlled environmental conditions. The results show that digitally collected plant traits, including digital shoot growth rate and digital senescence rate, can be used as proxy traits for selecting salinity-tolerant accessions. A haplotype-based genome-wide association study was conducted using 58,502 linkage disequilibrium-based haplotype blocks derived from 883,300 genome-wide SNPs and identified 95 QTL for salinity tolerance component traits, of which 54 were novel and 41 overlapped with previously reported QTL. Gene ontology analysis identified a suite of candidate genes for salinity tolerance, some of which are already known to play a role in stress tolerance in other plant species. This study identified wheat accessions that utilise different tolerance mechanisms and which can be used in future studies to investigate the genetic and genic basis of salinity tolerance. Our results suggest salinity tolerance has not arisen from or been bred into accessions from specific regions or groups. Rather, they suggest salinity tolerance is widespread, with small-effect genetic variants contributing to different levels of tolerance in diverse, locally adapted germplasm.

PMID:37375992 | DOI:10.3390/plants12122367

Pharmaceuticals (Basel). 2023 May 26;16(6):794. doi: 10.3390/ph16060794.

ABSTRACT

The serendipitous discovery of nanobodies (NBs) around two decades ago opened the door to new possibilities for innovative strategies, particularly in cancer treatment. These antigen-binding fragments are derived from heavy-chain-only antibodies naturally found in the serum of camelids and sharks. NBs are an appealing agent for the progress of innovative therapeutic strategies because they combine the advantageous assets of smaller molecules and conventional monoclonal antibodies (mAbs). Moreover, the possibility to produce NBs using bacterial systems reduces manufacturing expenses and speeds up the production process, making them a feasible option for the development of new bio-drugs. Several NBs have been developed over the past 10 years and are currently being tested in clinical trials for various human targets. Here, we provide an overview of the notable structural and biochemical characteristics of NBs, particularly in their application against HER2, an extracellular receptor that often gets aberrantly activated during breast cancer tumorigenesis. The focus is on the recent advancements in diagnostic and therapeutic research up to the present date.

PMID:37375741 | DOI:10.3390/ph16060794

Nutrients. 2023 Jun 12;15(12):2727. doi: 10.3390/nu15122727.

ABSTRACT

Vitamin K and vitamin K-dependent proteins have been reported to be associated with a large spectrum of age-related diseases. While most of these associations have been deduced from observational studies, solid evidence for the direct impact of vitamin K on cellular senescence remains to be proven. As vitamin K status reflects the complexity of interactions between dietary intake, gut microbiome activity and health, we will demonstrate the pivotal role of the diet-microbiome-health axis in human ageing and exemplify how vitamin K is implicated therein. We propose that food quality (i.e., food pattern) should be highlighted beyond the quantity of total vitamin K intake. Instead of focusing on a single nutrient, exploring a healthy diet containing vitamin K may be more strategic. As such, healthy eating patterns can be used to make dietary recommendations for the public. Emerging evidence suggests that dietary vitamin K is a modulator of the diet-microbiome-health axis, and this needs to be incorporated into the investigation of the impact of vitamin K on gut microbial composition and metabolic activities, along with host health outcomes. In addition, we highlight several critical caveats that need to be acknowledged regarding the interplay between diet, vitamin K, gut microbiome and host health that is pivotal for elucidating the role of vitamin K in ageing and responding to the urgent call of healthy eating concerning public health.

PMID:37375631 | DOI:10.3390/nu15122727

Microorganisms. 2023 Jun 6;11(6):1507. doi: 10.3390/microorganisms11061507.

ABSTRACT

As it is the case with natural substrates, artificial surfaces of man-made devices are home to a myriad of microbial species. Artificial products are not necessarily characterized by human-associated microbiomes; instead, they can present original microbial populations shaped by specific environmental-often extreme-selection pressures. This review provides a detailed insight into the microbial ecology of a range of artificial devices, machines, and appliances, which we argue are specific microbial niches that do not necessarily fit in the "build environment" microbiome definition. Instead, we propose here the Microbiome of Things (MoT) concept analogous to the Internet of Things (IoT) because we believe it may be useful to shed light on human-made, but not necessarily human-related, unexplored microbial niches.

PMID:37375009 | DOI:10.3390/microorganisms11061507

Microorganisms. 2023 May 31;11(6):1464. doi: 10.3390/microorganisms11061464.

ABSTRACT

Considering the ban on the use of antibiotics as growth stimulators in the livestock industry, the use of microbiota modulators appears to be an alternative solution to improve animal performance. This review aims to describe the effect of different families of modulators on the gastrointestinal microbiota of poultry, pigs and ruminants and their consequences on host physiology. To this end, 65, 32 and 4 controlled trials or systematic reviews were selected from PubMed for poultry, pigs and ruminants, respectively. Microorganisms and their derivatives were the most studied modulator family in poultry, while in pigs, the micronutrient family was the most investigated. With only four controlled trials selected for ruminants, it was difficult to conclude on the modulators of interest for this species. For some modulators, most studies showed a beneficial effect on both the phenotype and the microbiota. This was the case for probiotics and plants in poultry and minerals and probiotics in pigs. These modulators seem to be a good way for improving animal performance.

PMID:37374967 | DOI:10.3390/microorganisms11061464

Microorganisms. 2023 May 25;11(6):1389. doi: 10.3390/microorganisms11061389.

ABSTRACT

Mangroves provide a unique ecological environment for complex microbial communities, which play important roles in biogeochemical cycles, such as those for carbon, sulfur, and nitrogen. Microbial diversity analyses of these ecosystems help us understand the changes caused by external influences. Amazonian mangroves occupy an area of 9000 km2, corresponding to 70% of the mangroves in Brazil, on which studies of microbial biodiversity are extremely scarce. The present study aimed to determine changes in microbial community structure along the PA-458 highway, which fragmented a mangrove zone. Mangrove samples were collected from three zones, (i) degraded, (ii) in the process of recovery, and (iii) preserved. Total DNA was extracted and submitted for 16S rDNA amplification and sequencing on an MiSeq platform. Subsequently, reads were processed for quality control and biodiversity analyses. The most abundant phyla were Proteobacteria, Firmicutes, and Bacteroidetes in all three mangrove locations, but in significantly different proportions. We observed a considerable reduction in diversity in the degraded zone. Important genera involved in sulfur, carbon, and nitrogen metabolism were absent or dramatically reduced in this zone. Our results show that human impact in the mangrove areas, caused by the construction of the PA-458 highway, has resulted in a loss of biodiversity.

PMID:37374891 | DOI:10.3390/microorganisms11061389

Life (Basel). 2023 Jun 10;13(6):1364. doi: 10.3390/life13061364.

ABSTRACT

Atrial fibrillation (AF) is the most common type of sustained arrhythmia. The numerous gaps concerning the knowledge of its mechanism make improving clinical management difficult. As omics technologies allow more comprehensive insight into biology and disease at a molecular level, bioinformatics encompasses valuable tools for studying systems biology, as well as combining and modeling multi-omics data and networks. Network medicine is a subarea of network biology where disease traits are considered perturbations within the interactome. With this approach, potential disease drivers can be revealed, and the effect of drugs, novel or repurposed, used alone or in combination, may be studied. Thus, this work aims to review AF pathology from a network medicine perspective, helping researchers to comprehend the disease more deeply. Essential concepts involved in network medicine are highlighted, and specific research applying network medicine to study AF is discussed. Additionally, data integration through literature mining and bioinformatics tools, with network building, is exemplified. Together, all of the data show the substantial role of structural remodeling, the immune system, and inflammation in this disease etiology. Despite this, there are still gaps to be filled about AF.

PMID:37374146 | DOI:10.3390/life13061364

Life (Basel). 2023 Jun 1;13(6):1308. doi: 10.3390/life13061308.

ABSTRACT

BACKGROUND: Primary dysmenorrhea is considered to be one of the most common gynecological complaints, affecting women's daily activities and social life. The severity of dysmenorrhea varies among women, and its management is of high importance for them. Given that non-steroidal anti-inflammatory drugs (NSAIDs), the established treatment for dysmenorrhea, are associated with many adverse events, alternative therapeutic options are under evaluation. Emerging evidence correlates management of dysmenorrhea with micronutrients, especially vitamins.

PURPOSE: The aim of this narrative review is to highlight and provide evidence of the potential benefits of vitamins for the management of dysmenorrhea.

METHODS: The articles were searched on PubMed, Scopus and Google Scholar. The searching process was based on keywords, such as "primary dysmenorrhea", "vitamins", "supplementation", "vitamin D", "vitamin E" and others. Our search focused on data derived from clinical trials, published only during the last decade (older articles were excluded).

RESULTS: In this review, 13 clinical trials were investigated. Most of them supported the anti-inflammatory, antioxidant and analgesic properties of vitamins. Particularly, vitamins D and E revealed a desirable effect on dysmenorrhea relief Conclusion: Despite the scarcity and heterogeneity of related research, the studies indicate a role of vitamins for the management of primary dysmenorrhea, proposing that they should be considered as alternative therapeutic candidates for clinical use. Nevertheless, this correlation warrants further research.

PMID:37374091 | DOI:10.3390/life13061308

J Pers Med. 2023 Jun 5;13(6):956. doi: 10.3390/jpm13060956.

ABSTRACT

Chronic venous disease (CVD) is a common condition that affects the veins in the lower limbs, resulting in a variety of symptoms, such as swelling, pain, and varicose veins (VVs). The plenty hormonal, hemodynamic and mechanical changes occurred in pregnancy make women especially vulnerable to suffer from this condition in this period. Previous works have identified that CVD is associated with an increased inflammatory milieu and significant damage in maternofetal tissues, such as the umbilical cord. However, the inflammatory status of this structure in these patients has not been studied yet. Thus, the aim of the present study was to examine gene and protein expression of a set of inflammatory markers-Allograft inflammatory factor 1 (AIF-1), the proinflammatory cytokines interleukin 12A (IL-12A) and IL-18 and the anti-inflammatory product IL-10-in the umbilical cord of women with CVD during pregnancy (N = 62) and healthy pregnant women (HC; N = 52) by the use of real time qPCR and immunohistochemistry (IHC). Our results demonstrate that the umbilical cord tissue from CVD women exhibit an increased expression of AIF-1, IL-12A and IL-18 along with a decrease in IL-10. Therefore, our study suggests an inflammatory status of this structure related to CVD. Further studies should be conducted to evaluate the expression of other inflammatory markers, as well as to analyze the maternofetal impact of these findings.

PMID:37373945 | DOI:10.3390/jpm13060956

Int J Mol Sci. 2023 Jun 19;24(12):10348. doi: 10.3390/ijms241210348.

ABSTRACT

One of the major challenges in cancer therapy lies in the limited targeting specificity exhibited by existing anti-cancer drugs. Tumor-homing peptides (THPs) have emerged as a promising solution to this issue, due to their capability to specifically bind to and accumulate in tumor tissues while minimally impacting healthy tissues. THPs are short oligopeptides that offer a superior biological safety profile, with minimal antigenicity, and faster incorporation rates into target cells/tissues. However, identifying THPs experimentally, using methods such as phage display or in vivo screening, is a complex, time-consuming task, hence the need for computational methods. In this study, we proposed StackTHPred, a novel machine learning-based framework that predicts THPs using optimal features and a stacking architecture. With an effective feature selection algorithm and three tree-based machine learning algorithms, StackTHPred has demonstrated advanced performance, surpassing existing THP prediction methods. It achieved an accuracy of 0.915 and a 0.831 Matthews Correlation Coefficient (MCC) score on the main dataset, and an accuracy of 0.883 and a 0.767 MCC score on the small dataset. StackTHPred also offers favorable interpretability, enabling researchers to better understand the intrinsic characteristics of THPs. Overall, StackTHPred is beneficial for both the exploration and identification of THPs and facilitates the development of innovative cancer therapies.

PMID:37373494 | DOI:10.3390/ijms241210348