NPJ Biofilms Microbiomes. 2025 Jan 8;11(1):6. doi: 10.1038/s41522-024-00639-w.

ABSTRACT

This study aims to evaluate differences in gut microbiota structures between infertile women undergoing frozen embryo transfer (FET) with gestational diabetes mellitus (GDM) and healthy controls (HCs), and to identify potential markers. We comprehensively enrolled 193 infertile women undergoing FET (discovery cohort: 38 HCs and 31 GDM; validation cohort: 85 HCs and 39 GDM). Gut microbial profiles of the discovery cohort were investigated during the pre-pregnancy (Pre), first trimester (T1), and second trimester (T2). The microbial community in the HCs group remained relatively stable throughout the pregnancy, while the microbial structure alteration occurred in the GDM group during T2. A model based on ten bacteria and ten metabolites simultaneously was used to predict the risk of GDM developing in the pre-pregnancy state with the ROC value of 0.712. Algorithms on the basis of marker species and biochemical parameters can be used as effective tools for GDM risk evaluation before pregnancy.

PMID:39779730 | DOI:10.1038/s41522-024-00639-w

Nat Commun. 2025 Jan 8;16(1):498. doi: 10.1038/s41467-024-55660-6.

ABSTRACT

Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor inhibition together with multiomics to unveil the processes underlying oral epithelial progenitor cell reprogramming into tumor initiating cells at single cell resolution. Tumor initiating cells displayed a distinct stem-like state, defined by aberrant proliferative, hypoxic, squamous differentiation, and partial epithelial to mesenchymal invasive gene programs. YAP-mediated tumor initiating cell programs included activation of oncogenic transcriptional networks and mTOR signaling, and recruitment of myeloid cells to the invasive front contributing to tumor infiltration. Tumor initiating cell transcriptional programs are conserved in human head and neck cancer and associated with poor patient survival. These findings illuminate processes underlying cancer initiation at single cell resolution, and identify candidate targets for early cancer detection and prevention.

PMID:39779672 | DOI:10.1038/s41467-024-55660-6

Med Oncol. 2025 Jan 8;42(2):41. doi: 10.1007/s12032-024-02560-w.

ABSTRACT

CRC has the third-highest cancer incidence and death. Many human cancers, including colorectal cancer, are connected to abnormal signaling pathway gene expression. Many human malignancies include Hippo and Rap1 signaling. This research examined curcumin's therapeutic effects on colorectal cancer cell lines' Hippo and Rap1 signaling pathway genes. The role of the above signaling pathways is considered in colorectal cancer development. No research has examined curcumin's influence on key genes in these pathways; thus, this work is meant to uncover its more precise mechanism. First, the gene expression omnibus database is queried to discover GSE8671, a dataset that contains differentially expressed genes associated in CRC formation. DAVID was used to discover the corporation of these genes and signaling pathways (Hippo and Rap1), and the cancer genome atlas (TCGA) database was utilized to select genes and assess their expression and biomarker potential. MTT, apoptosis, and quantitative PCR were used to assess whether curcumin is therapeutic for colorectal cancer cell lines. An in-silico analysis identified the dysregulation of several critical genes AXIN2, MYC, TEAD4, MET, LPAR1, and ADCY9 in colorectal cancer, highlighting their involvement in the Hippo and Rap1 signaling pathways. Experimental assessments, including MTT assays, apoptosis assays, and quantitative PCR (qPCR) analysis, demonstrated that the targeted modulation of these genes effectively inhibits cancer cell proliferation. Specifically, treatment with curcumin resulted in a significant reduction in cell viability in HT-29 and HCT-116 colorectal cancer cell lines, thereby facilitating apoptotic cell death. Furthermore, curcumin administration was associated with the upregulation of LPAR1 and ADCY9 gene expression, while concurrently downregulating AXIN2, MYC, TEAD4, and MET in both cell lines. This study reveals compelling evidence of curcumin's potent anticancer properties, highlighting its transformative influence on the Hippo and Rap1 signaling pathways within colorectal cancer cells. These findings not only underscore curcumin's potential as a therapeutic agent but also pave the way for innovative strategies in the fight against colorectal cancer.

PMID:39779534 | DOI:10.1007/s12032-024-02560-w

Nucleic Acids Res. 2025 Jan 7;53(1):gkae1235. doi: 10.1093/nar/gkae1235.

ABSTRACT

Dinucleases of the DEDD superfamily, such as oligoribonuclease, Rexo2 and nanoRNase C, catalyze the essential final step of RNA degradation, the conversion of di- to mononucleotides. The active sites of these enzymes are optimized for substrates that are two nucleotides long, and do not discriminate between RNA and DNA. Here, we identified a novel DEDD subfamily, members of which function as dedicated deoxydinucleases (diDNases) that specifically hydrolyze single-stranded DNA dinucleotides in a sequence-independent manner. Crystal structures of enzyme-substrate complexes reveal that specificity for DNA stems from a combination of conserved structural elements that exclude diribonucleotides as substrates. Consistently, diDNases fail to complement the loss of enzymes that act on diribonucleotides, indicating that these two groups of enzymes support distinct cellular functions. The genes encoding diDNases are found predominantly in genomic islands of Actinomycetes and Clostridia, which, together with their association with phage-defense systems, suggest potential roles in bacterial immunity.

PMID:39778863 | DOI:10.1093/nar/gkae1235

Planta Med. 2025 Jan 8. doi: 10.1055/a-2512-8928. Online ahead of print.

ABSTRACT

In recent years, the incidence of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, has shown a steadily rising trend, which has posed a major challenge to the global public health. Traditional Chinese Medicine (TCM), with its multi-component and multi-target characteristics, offers a promising approach for the treatment of neurodegenerative diseases. However, it is difficult to comprehensively elucidate the complex mechanisms underlying TCM formulations. As an emerging systems biology approach, network pharmacology has provided a crucial tool for uncovering the multi-target mechanisms of TCM through high-throughput technologies, molecular docking, and network analysis. This paper reviews the advancements in the application of network pharmacology in treating neurodegenerative diseases with TCM, analyzes the current status of relevant databases and technological methods, discusses the limitations in the research, and proposes future directions to promote the modernization of TCM and the development of precision medicine. Keywords: Neurodegenerative diseases, Traditional Chinese Medicine, Network pharmacology, Therapeutic targets.

PMID:39778593 | DOI:10.1055/a-2512-8928

Cell Syst. 2024 Dec 31:101163. doi: 10.1016/j.cels.2024.12.004. Online ahead of print.

ABSTRACT

Deep learning is a promising strategy for modeling cis-regulatory elements. However, models trained on genomic sequences often fail to explain why the same transcription factor can activate or repress transcription in different contexts. To address this limitation, we developed an active learning approach to train models that distinguish between enhancers and silencers composed of binding sites for the photoreceptor transcription factor cone-rod homeobox (CRX). After training the model on nearly all bound CRX sites from the genome, we coupled synthetic biology with uncertainty sampling to generate additional rounds of informative training data. This allowed us to iteratively train models on data from multiple rounds of massively parallel reporter assays. The ability of the resulting models to discriminate between CRX sites with identical sequence but opposite functions establishes active learning as an effective strategy to train models of regulatory DNA. A record of this paper's transparent peer review process is included in the supplemental information.

PMID:39778579 | DOI:10.1016/j.cels.2024.12.004

PLoS Pathog. 2025 Jan 8;21(1):e1012823. doi: 10.1371/journal.ppat.1012823. Online ahead of print.

ABSTRACT

Malaria parasites must respond quickly to environmental changes, including during their transmission between mammalian and mosquito hosts. Therefore, female gametocytes proactively produce and translationally repress mRNAs that encode essential proteins that the zygote requires to establish a new infection. While the release of translational repression of individual mRNAs has been documented, the details of the global release of translational repression have not. Moreover, changes in the spatial arrangement and composition of the DOZI/CITH/ALBA complex that contribute to translational control are also not known. Therefore, we have conducted the first quantitative, comparative transcriptomics and DIA-MS proteomics of Plasmodium parasites across the host-to-vector transmission event to document the global release of translational repression. Using female gametocytes and zygotes of P. yoelii, we found that ~200 transcripts are released for translation soon after fertilization, including those encoding essential functions. Moreover, we identified that many transcripts remain repressed beyond this point. TurboID-based proximity proteomics of the DOZI/CITH/ALBA regulatory complex revealed substantial spatial and/or compositional changes across this transmission event, which are consistent with recent, paradigm-shifting models of translational control. Together, these data provide a model for the essential translational control mechanisms that promote Plasmodium's efficient transmission from mammalian host to mosquito vector.

PMID:39777415 | DOI:10.1371/journal.ppat.1012823

Synth Syst Biotechnol. 2024 Jul 30;9(4):861-870. doi: 10.1016/j.synbio.2024.07.006. eCollection 2024 Dec.

ABSTRACT

Saccharomyces cerevisiae, a widely utilized model organism, has seen continuous updates to its genome-scale metabolic model (GEM) to enhance the prediction performance for metabolic engineering and systems biology. This study presents an auxotrophy-based curation of the yeast GEM, enabling facile upgrades to yeast GEMs in future endeavors. We illustrated that the curation bolstered the predictive capability of the yeast GEM particularly in predicting auxotrophs without compromising accuracy in other simulations, and thus could be an effective manner for GEM refinement. Last, we leveraged the curated yeast GEM to systematically predict auxotrophs, thereby furnishing a valuable reference for the design of nutrient-dependent cell factories and synthetic yeast consortia.

PMID:39777162 | PMC:PMC11704421 | DOI:10.1016/j.synbio.2024.07.006

Patterns (N Y). 2024 Dec 6;5(12):101115. doi: 10.1016/j.patter.2024.101115. eCollection 2024 Dec 13.

ABSTRACT

Guidelines in statistical modeling for genomics hold that simpler models have advantages over more complex ones. Potential advantages include cost, interpretability, and improved generalization across datasets or biological contexts. We directly tested the assumption that small gene signatures generalize better by examining the generalization of mutation status prediction models across datasets (from cell lines to human tumors and vice versa) and biological contexts (holding out entire cancer types from pan-cancer data). We compared model selection between solely cross-validation performance and combining cross-validation performance with regularization strength. We did not observe that more regularized signatures generalized better. This result held across both generalization problems and for both linear models (LASSO logistic regression) and non-linear ones (neural networks). When the goal of an analysis is to produce generalizable predictive models, we recommend choosing the ones that perform best on held-out data or in cross-validation instead of those that are smaller or more regularized.

PMID:39776849 | PMC:PMC11701843 | DOI:10.1016/j.patter.2024.101115

Theranostics. 2025 Jan 1;15(3):1094-1109. doi: 10.7150/thno.96488. eCollection 2025.

ABSTRACT

Rationale: The mannose receptor (CD206, expressed by the gene Mrc1) is a surface marker overexpressed by anti-inflammatory and pro-tumoral macrophages. As such, CD206+ macrophages play key roles in the immune response to different pathophysiological conditions and represent a promising diagnostic and therapeutic target. However, methods to specifically target these cells remain challenging. In this study, we describe a multi-mannose approach to develop CD206-targeting fluorescent and MRI agents that specifically and sensitively detect and monitor CD206+ macrophage immune response in different disease conditions. Methods: We designed and synthesized fluorescent agents MR1-cy5 and MR2-cy5, and MRI agents Mann2-DTPA-Gd and MannGdFish. Cellular assays using pro-inflammatory and anti-inflammatory macrophages differentiated from RAW 264.7 cells were performed, and signals were detected by fluorescence microscopy and inductively coupled plasma mass spectrometry (ICP-MS) to validate specificity in vitro. In vivo specificity and efficacy of the agents were evaluated by MRI in a subcutaneous wound healing model and experimental glioma with Mrc1 +/+ without and with D-mannose treatment, Mrc1 +/-, and Mrc1 -/- mice, and in stroke. One-way ANOVA and two-way ANOVA tests were used for data analysis. P < 0.05 was considered statistically different. Results: Both in vitro fluorescence imaging with MR2-cy5, ICP-MS with Mann2-DTPA-Gd, and in vivo MRI in Mrc1 -/- mice confirmed the specificity of our approach. Mann2-DTPA-Gd MRI can track the changes of CD206+ macrophages at different stages of wound healing, correlating well with flow cytometry data using another anti-inflammatory macrophage marker (arginase-1). The specificity and efficacy of Mann2-DPTA-Gd were further validated in experimental glioma, in which Mann2-DTPA-Gd imaging detected CD206+ tumor-associated macrophages (TAMs), demonstrated significantly decreased signals in Mrc1 +/- mice and Mrc1 -/- mice, and tracked treatment changes in D-mannose-treated Mrc1 +/+ mice. Furthermore, Mann2-DTPA-Gd can report microglia/macrophages and correlate with histology in stroke. The more Gd-stable agent MannGdFish demonstrated similar efficacy as Mann2-DTPA-Gd in vivo with favorable biodistribution and pharmacokinetics. Conclusion: We have developed a fluorescent agent (MR2-cy5) and MRI agents (Mann2-DTPA-Gd and MannGdFish) with two mannose moieties that are highly specific to CD206 and can track CD206+ macrophages in disease models of wound healing, tumor, and neurological disease. Importantly, MannGdFish, with its high specificity, stability, favorable biodistribution, and pharmacokinetics, is a promising translational candidate to noninvasively monitor CD206+ macrophages in repair/regeneration and tumors in patients. In addition, with the specific binding motif to CD206, other imaging modalities and therapeutic agents could also be introduced for theranostic applications.

PMID:39776805 | PMC:PMC11700851 | DOI:10.7150/thno.96488

JBMR Plus. 2024 Dec 10;9(2):ziae159. doi: 10.1093/jbmrpl/ziae159. eCollection 2025 Feb.

ABSTRACT

Human genetic studies have nominated cadherin-like and PC-esterase domain-containing 1 (CPED1) as a candidate target gene mediating bone mineral density (BMD) and fracture risk heritability. Recent efforts to define the role of CPED1 in bone in mouse and human models have revealed complex alternative splicing and inconsistent results arising from gene targeting, making its function in bone difficult to interpret. To better understand the role of CPED1 in adult bone mass and morphology, we conducted a comprehensive genetic and phenotypic analysis of cped1 in zebrafish, an emerging model for bone and mineral research. We analyzed two different cped1 mutant lines and performed deep phenotyping to characterize more than 200 measures of adult vertebral, craniofacial, and lean tissue morphology. We also examined alternative splicing of zebrafish cped1 and gene expression in various cell/tissue types. Our studies fail to support an essential role of cped1 in adult zebrafish bone. Specifically, homozygous mutants for both cped1 mutant alleles, which are expected to result in loss-of-function and impact all cped1 isoforms, exhibited no significant differences in the measures examined when compared to their respective wildtype controls, suggesting that cped1 does not significantly contribute to these traits. We identified sequence differences in critical residues of the catalytic triad between the zebrafish and mouse orthologs of CPED1, suggesting that differences in key residues, as well as distinct alternative splicing, could underlie different functions of CPED1 orthologs in the two species. Our studies fail to support a requirement of cped1 in zebrafish bone and lean tissue, adding to evidence that variants at 7q31.31 can act independently of CPED1 to influence BMD and fracture risk.

PMID:39776615 | PMC:PMC11701521 | DOI:10.1093/jbmrpl/ziae159

Gut Microbiome (Camb). 2024 May 31;5:e7. doi: 10.1017/gmb.2024.5. eCollection 2024.

ABSTRACT

Breastfeeding represents a strong selective factor for shaping the infant gut microbiota. Besides providing nutritional requirements for the infant, human milk is a key source of oligosaccharides, human milk oligosaccharides (HMOs), and diverse microbes in early life. This study aimed to evaluate the influence of human milk microbiota and oligosaccharides on the composition of infant faecal microbiota at one, three, and nine months postpartum. We profiled milk microbiota, HMOs, and infant faecal microbiota from 23 mother-infant pairs at these time points. The predominant genera in milk samples were Streptococcus, Staphylococcus, and an unclassified Enterobacteriaceae genus-level taxon (Enterobacteriaceae uncl.), whereas the infant faecal microbiota was predominated by Bifidobacterium, Bacteroides, and Enterobacteriaceae uncl. Mother-infant dyads frequently shared bacterial amplicon sequence variants (ASVs) belonging to the genera Bifidobacterium, Streptococcus, Enterobacteriaceae uncl., Veillonella, Bacteroides, and Haemophilus. The individual HMO concentrations in the milk showed either no change or decreased over the lactation period, except for 3-fucosyllactose (3-FL), which increased. Neither maternal secretor status nor HMO concentrations were significantly associated with microbiota composition at the different ages or the bacterial ASVs of maternal milk and infant faeces. This study suggests an age-dependent role of milk microbes in shaping the gut microbiota, while variations in HMO concentrations show limited influence.

PMID:39776540 | PMC:PMC11706684 | DOI:10.1017/gmb.2024.5

Lab Chip. 2025 Jan 8. doi: 10.1039/d4lc00779d. Online ahead of print.

ABSTRACT

Point-of-care testing (POCT) holds significant importance in the field of infectious disease prevention and control, as well as personalized precision medicine. The emerging microfluidics, capable of minimal reagent consumption, integration, and a high degree of automation, play a pivotal role in POCT. Centrifugal microfluidics, also termed lab-on-a-disc (LOAD), is a significant subfield of microfluidics that integrates crucial analytical steps onto a single chip, thereby optimizing the process and enabling high-throughput, automated analysis. By utilizing rotational mechanics to precisely control fluid dynamics without external pressure sources, centrifugal microfluidics facilitates swift operations ideal for urgent medical and field settings. This review provides a comprehensive overview of the latest advancements in centrifugal microfluidics for POCT, covering both theoretical principles and practical applications. We begin by introducing the fundamental operational principles, fluidic control mechanisms, and signal output detection methods. Subsequently, we delve into the typical applications of centrifugal microfluidic platforms in immunoassays, nucleic acid testing, antimicrobial susceptibility testing, and other tests. We also discuss the strengths and potential limitations of centrifugal microfluidic platforms, underscoring their transformative impact on traditional conventional procedures and their significant role in diagnostic practices.

PMID:39776118 | DOI:10.1039/d4lc00779d

Naturwissenschaften. 2025 Jan 8;112(1):5. doi: 10.1007/s00114-024-01950-4.

ABSTRACT

Physiological or genetic assays and computational modeling are valuable tools for understanding animals' visual discrimination capabilities. Yet sometimes, the results generated by these methods appear not to jive with other aspects of an animal's appearance or natural history, and behavioral confirmatory tests are warranted. Here we examine the peculiar case of a male jumping spider that displays red, black, white, and UV color patches during courtship despite the fact that, according to microspectrophotometry and color vision modeling, they are unlikely able to discriminate red from black. To test whether some optical or neurological component could have been missed using these methods, we conduct mate choice experiments. Some females are presented with a choice between males with their red leg coloration painted over with either red or black paint, while other females are presented with a choice between males with the same coloration painted over by either red or white paint. This latter pairing of red and white males should have been easily distinguishable to the spiders and served as a control to ensure our experimental setup was conducive to natural mating behavior. Red males were more likely to mate than white males (P = 0.035), whereas red and black males had identical mating success (P = 1.0). This suggests that previous physiological and computational work on these spiders was correct in concluding that they are unable to discriminate between red and black. Any functional significance of displaying both colors, rather than only black, remains unresolved.

PMID:39775916 | DOI:10.1007/s00114-024-01950-4

Bioinformatics. 2025 Jan 7:btaf005. doi: 10.1093/bioinformatics/btaf005. Online ahead of print.

ABSTRACT

MOTIVATION: The identification of biologically meaningful domains is a central step in the analysis of spatial transcriptomic data.

RESULTS: Following Occam's razor, we show that a simple PCA-based algorithm for unsupervised spatial domain identification rivals the performance of ten competing state-of-the-art methods across six single-cell spatial transcriptomic datasets. Our reductionist approach, NichePCA, provides researchers with intuitive domain interpretation and excels in execution speed, robustness, and scalability.

AVAILABILITY AND IMPLEMENTATION: The code is available at https://github.com/imsb-uke/nichepca.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:39775801 | DOI:10.1093/bioinformatics/btaf005

Int J Comput Assist Radiol Surg. 2025 Jan 7. doi: 10.1007/s11548-024-03310-z. Online ahead of print.

ABSTRACT

PURPOSE: Lung fissure segmentation on CT images often relies on 3D convolutional neural networks (CNNs). However, 3D-CNNs are inefficient for detecting thin structures like the fissures, which make up a tiny fraction of the entire image volume. We propose to make lung fissure segmentation more efficient by using geometric deep learning (GDL) on sparse point clouds.

METHODS: We abstract image data with sparse keypoint (KP) clouds. We train GDL models to segment the point cloud, comparing three major paradigms of models (PointNets, graph convolutional networks (GCNs), and PointTransformers). From the sparse point segmentations, 3D meshes of the objects are reconstructed to obtain a dense surface. The state-of-the-art Poisson surface reconstruction (PSR) makes up most of the time in our pipeline. Therefore, we propose an efficient point cloud to mesh autoencoder (PC-AE) that deforms a template mesh to fit a point cloud in a single forward pass. Our pipeline is evaluated extensively and compared to the 3D-CNN gold standard nnU-Net on diverse clinical and pathological data.

RESULTS: GCNs yield the best trade-off between inference time and accuracy, being 21 × faster with only 1.4 × increased error over the nnU-Net. Our PC-AE also achieves a favorable trade-off, being 3 × faster at 1.5 × the error compared to the PSR.

CONCLUSION: We present a KP-based fissure segmentation pipeline that is more efficient than 3D-CNNs and can greatly speed up large-scale analyses. A novel PC-AE for efficient mesh reconstruction from sparse point clouds is introduced, showing promise not only for fissure segmentation. Source code is available on https://github.com/kaftanski/fissure-segmentation-IJCARS.

PMID:39775630 | DOI:10.1007/s11548-024-03310-z

Eur J Clin Microbiol Infect Dis. 2025 Jan 7. doi: 10.1007/s10096-024-05030-3. Online ahead of print.

ABSTRACT

PURPOSE: We designed and tested a point of care test panel to detect E.coli and antibiotic susceptibility in urine samples from patients at the point of care in the urological department. The aim of this approach is to facilitate choosing an appropriate antibiotic for urinary tract infections (UTI) at first presentation in the context of increasing antibiotic resistance in uropathogens worldwide.

METHODS: We analyzed 162 E.coli isolates from samples from a university urological department to determine phenotypic and genotypic resistance data. With this data we created customized LAMP (loop-mediated isothermal amplification) panels for a commercial machine with which to detect and possibly quantify E.coli and six antibiotic resistance determinants. In a second step we tested these panel(s) for diagnostic accuracy on 1596 urine samples and compared with routine microbiological culture.

RESULTS: E.coli was detected with 95.4% sensitivity and 96.1% specificity. Dynamics of the LAMP amplification could be used to gauge bacterial loads in the samples. Antibiotic sensitivity was detected with good negative (sensitive) predictive values: ampicillin 92.8%, ampicillin/sulbactam 96.4%, cefuroxime 92.8%, cefotaxime 97.8%, trimethoprim/sulfamethoxazole 96.5%, ciprofloxacin 96.8%.

CONCLUSION: The LAMP panel provided E.coli detection and sensitivity information within one hour and thus could principally guide initial antibiotic therapy upon patients presenting with UTI. The panel helps to select initial adequate antibiotic therapy as well as providing diagnostic stewardship. Follow up investigations will expand the test system to other uropathogens.

PMID:39775368 | DOI:10.1007/s10096-024-05030-3

PLoS Comput Biol. 2024 Dec 30;20(12):e1012653. doi: 10.1371/journal.pcbi.1012653. Online ahead of print.

ABSTRACT

Phylogenies depicting the evolutionary history of genetically heterogeneous subpopulations of cells from the same cancer, i.e., cancer phylogenies, offer valuable insights about cancer development and guide treatment strategies. Many methods exist that reconstruct cancer phylogenies using point mutations detected with bulk DNA sequencing. However, these methods become inaccurate when reconstructing phylogenies with more than 30 mutations, or, in some cases, fail to recover a phylogeny altogether. Here, we introduce Orchard, a cancer phylogeny reconstruction algorithm that is fast and accurate using up to 1000 mutations. Orchard samples without replacement from a factorized approximation of the posterior distribution over phylogenies, a novel result derived in this paper. Each factor in this approximate posterior corresponds to a conditional distribution for adding a new mutation to a partially built phylogeny. Orchard optimizes each factor sequentially, generating a sequence of incrementally larger phylogenies that ultimately culminate in a complete tree containing all mutations. Our evaluations demonstrate that Orchard outperforms state-of-the-art cancer phylogeny reconstruction methods in reconstructing more plausible phylogenies across 90 simulated cancers and 14 B-progenitor acute lymphoblastic leukemias (B-ALLs). Remarkably, Orchard accurately reconstructs cancer phylogenies using up to 1,000 mutations. Additionally, we demonstrate that the large and accurate phylogenies reconstructed by Orchard are useful for identifying patterns of somatic mutations and genetic variations among distinct cancer cell subpopulations.

PMID:39775053 | DOI:10.1371/journal.pcbi.1012653

Nat Commun. 2025 Jan 7;16(1):441. doi: 10.1038/s41467-024-55593-0.

ABSTRACT

New and more transmissible variants of SARS-CoV-2 have arisen multiple times over the course of the pandemic. Rapidly identifying mutations that affect transmission could improve our understanding of viral biology and highlight new variants that warrant further study. Here we develop a generic, analytical epidemiological model to infer the transmission effects of mutations from genomic surveillance data. Applying our model to SARS-CoV-2 data across many regions, we find multiple mutations that substantially affect the transmission rate, both within and outside the Spike protein. The mutations that we infer to have the largest effects on transmission are strongly supported by experimental evidence from prior studies. Importantly, our model detects lineages with increased transmission even at low frequencies. As an example, we infer significant transmission advantages for the Alpha, Delta, and Omicron variants shortly after their appearances in regional data, when they comprised only around 1-2% of sample sequences. Our model thus facilitates the rapid identification of variants and mutations that affect transmission from genomic surveillance data.

PMID:39774959 | DOI:10.1038/s41467-024-55593-0

Nat Commun. 2025 Jan 7;16(1):461. doi: 10.1038/s41467-025-55872-4.

ABSTRACT

The dual challenges of global population explosion and environmental deterioration represent major hurdles for 21st Century agriculture culminating in an unprecedented demand for food security. In this Review, we revisit historical concepts of plasticity and canalization before integrating them with contemporary studies of genotype-environment interactions (G×E) that are currently being carried out at the genome-wide level. In doing so we address both fundamental questions regarding G×E and potential strategies to best secure yields in both current and future climate scenarios.

PMID:39774717 | DOI:10.1038/s41467-025-55872-4