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1.
Nanoscale ; 16(23): 10947-10974, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38804109

ABSTRACT

Colloidal quantum dots (CQDs) have been a hot research topic ever since they were successfully fabricated in 1993 via the hot injection method. The Nobel Prize in Chemistry 2023 was awarded to Moungi G. Bawendi, Louis E. Brus and Alexei I. Ekimov for the discovery and synthesis of quantum dots. The Internet of Things (IoT) has also attracted a lot of attention due to the technological advancements and digitalisation of the world. This review first aims to give the basics behind QD physics. After that, the history behind CQD synthesis and the different methods used to synthesize most widely researched CQD materials (CdSe, PbS and InP) are revisited. A brief introduction to what IoT is and how it works is also mentioned. Then, the most widely researched CQD devices that can be used for the main IoT components are reviewed, where the history, physics, the figures of merit (FoMs) and the state-of-the-art are discussed. Finally, the challenges and different methods for integrating CQDs into IoT devices are discussed, mentioning the future possibilities that await CQDs.

2.
Brief Bioinform ; 24(6)2023 09 22.
Article in English | MEDLINE | ID: mdl-37930031

ABSTRACT

Reconstructing the full-length sequence of extrachromosomal circular DNA (eccDNA) from short sequencing reads has proved challenging given the similarity of eccDNAs and their corresponding linear DNAs. Previous sequencing methods were unable to achieve high-throughput detection of full-length eccDNAs. Herein, a novel algorithm was developed, called Full-Length eccDNA Detection (FLED), to reconstruct the sequence of eccDNAs based on the strategy that combined rolling circle amplification and nanopore long-reads sequencing technology. Seven human epithelial and cancer cell line samples were analyzed by FLED and over 5000 full-length eccDNAs were identified per sample. The structures of identified eccDNAs were validated by both Polymerase Chain Reaction (PCR) and Sanger sequencing. Compared to other published nanopore-based eccDNA detectors, FLED exhibited higher sensitivity. In cancer cell lines, the genes overlapped with eccDNA regions were enriched in cancer-related pathways and cis-regulatory elements can be predicted in the upstream or downstream of intact genes on eccDNA molecules, and the expressions of these cancer-related genes were dysregulated in tumor cell lines, indicating the regulatory potency of eccDNAs in biological processes. The proposed method takes advantage of nanopore long reads and enables unbiased reconstruction of full-length eccDNA sequences. FLED is implemented using Python3 which is freely available on GitHub (https://github.com/FuyuLi/FLED).


Subject(s)
DNA, Circular , DNA , Humans , DNA/genetics , Polymerase Chain Reaction , Cell Line
3.
Comput Struct Biotechnol J ; 21: 4432-4445, 2023.
Article in English | MEDLINE | ID: mdl-37731598

ABSTRACT

Highly transcribed noncoding elements (HTNEs) are critical noncoding elements with high levels of transcriptional capacity in particular cohorts involved in multiple cellular biological processes. Investigation of HTNEs with persistent aberrant expression in abnormal tissues could be of benefit in exploring their roles in disease occurrence and progression. Breast cancer is a highly heterogeneous disease for which early screening and prognosis are exceedingly crucial. In this study, we developed a HTNE identification framework to systematically investigate HTNE landscapes in breast cancer patients and identified over ten thousand HTNEs. The robustness and rationality of our framework were demonstrated via public datasets. We revealed that HTNEs had significant chromatin characteristics of enhancers and long noncoding RNAs (lncRNAs) and were significantly enriched with RNA-binding proteins as well as targeted by miRNAs. Further, HTNE-associated genes were significantly overexpressed and exhibited strong correlations with breast cancer. Ultimately, we explored the subtype-specific transcriptional processes associated with HTNEs and uncovered the HTNE signatures that could classify breast cancer subtypes based on the properties of hormone receptors. Our results highlight that the identified HTNEs as well as their associated genes play crucial roles in breast cancer progression and correlate with subtype-specific transcriptional processes of breast cancer.

4.
Invest Radiol ; 58(10): 754-765, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37222527

ABSTRACT

OBJECTIVES: In multiple myeloma and its precursor stages, plasma cell infiltration (PCI) and cytogenetic aberrations are important for staging, risk stratification, and response assessment. However, invasive bone marrow (BM) biopsies cannot be performed frequently and multifocally to assess the spatially heterogenous tumor tissue. Therefore, the goal of this study was to establish an automated framework to predict local BM biopsy results from magnetic resonance imaging (MRI). MATERIALS AND METHODS: This retrospective multicentric study used data from center 1 for algorithm training and internal testing, and data from center 2 to 8 for external testing. An nnU-Net was trained for automated segmentation of pelvic BM from T1-weighted whole-body MRI. Radiomics features were extracted from these segmentations, and random forest models were trained to predict PCI and the presence or absence of cytogenetic aberrations. Pearson correlation coefficient and the area under the receiver operating characteristic were used to evaluate the prediction performance for PCI and cytogenetic aberrations, respectively. RESULTS: A total of 672 MRIs from 512 patients (median age, 61 years; interquartile range, 53-67 years; 307 men) from 8 centers and 370 corresponding BM biopsies were included. The predicted PCI from the best model was significantly correlated ( P ≤ 0.01) to the actual PCI from biopsy in all internal and external test sets (internal test set: r = 0.71 [0.51, 0.83]; center 2, high-quality test set: r = 0.45 [0.12, 0.69]; center 2, other test set: r = 0.30 [0.07, 0.49]; multicenter test set: r = 0.57 [0.30, 0.76]). The areas under the receiver operating characteristic of the prediction models for the different cytogenetic aberrations ranged from 0.57 to 0.76 for the internal test set, but no model generalized well to all 3 external test sets. CONCLUSIONS: The automated image analysis framework established in this study allows for noninvasive prediction of a surrogate parameter for PCI, which is significantly correlated to the actual PCI from BM biopsy.


Subject(s)
Deep Learning , Multiple Myeloma , Male , Humans , Middle Aged , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/genetics , Bone Marrow/diagnostic imaging , Retrospective Studies , Magnetic Resonance Imaging/methods , Biopsy , Chromosome Aberrations
5.
Cancers (Basel) ; 15(8)2023 Apr 17.
Article in English | MEDLINE | ID: mdl-37190266

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide, and the pronounced intra- and inter-tumor heterogeneity restricts clinical benefits. Dissecting molecular heterogeneity in HCC is commonly explored by endoscopic biopsy or surgical forceps, but invasive tissue sampling and possible complications limit the broadeer adoption. The radiomics framework is a promising non-invasive strategy for tumor heterogeneity decoding, and the linkage between radiomics and immuno-oncological characteristics is worth further in-depth study. In this study, we extracted multi-view imaging features from contrast-enhanced CT (CE-CT) scans of HCC patients, followed by developing a fused imaging feature subtyping (FIFS) model to identify two distinct radiomics subtypes. We observed two subtypes of patients with distinct texture-dominated radiomics profiles and prognostic outcomes, and the radiomics subtype identified by FIFS model was an independent prognostic factor. The heterogeneity was mainly attributed to inflammatory pathway activity and the tumor immune microenvironment. The predominant radiogenomics association was identified between texture-related features and immune-related pathways by integrating network analysis, and was validated in two independent cohorts. Collectively, this work described the close connections between multi-view radiomics features and immuno-oncological characteristics in HCC, and our integrative radiogenomics analysis strategy may provide clues to non-invasive inflammation-based risk stratification.

6.
Cancers (Basel) ; 14(22)2022 Nov 09.
Article in English | MEDLINE | ID: mdl-36428600

ABSTRACT

Background: This study aimed to reveal the heterogeneity of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of breast cancer (BC) and identify its prognosis values and molecular characteristics. Methods: Two radiogenomics cohorts (n = 246) were collected and tumor regions were segmented semi-automatically. A total of 174 radiomics features were extracted, and the imaging subtypes were identified and validated by unsupervised analysis. A gene-profile-based classifier was developed to predict the imaging subtypes. The prognostic differences and the biological and microenvironment characteristics of subtypes were uncovered by bioinformatics analysis. Results: Three imaging subtypes were identified and showed high reproducibility. The subtypes differed remarkably in tumor sizes and enhancement patterns, exhibiting significantly different disease-free survival (DFS) or overall survival (OS) in the discovery cohort (p = 0.024) and prognosis datasets (p ranged from <0.0001 to 0.0071). Large sizes and rapidly enhanced tumors usually had the worst outcomes. Associations were found between imaging subtypes and the established subtypes or clinical stages (p ranged from <0.001 to 0.011). Imaging subtypes were distinct in cell cycle and extracellular matrix (ECM)-receptor interaction pathways (false discovery rate, FDR < 0.25) and different in cellular fractions, such as cancer-associated fibroblasts (p < 0.05). Conclusions: The imaging subtypes had different clinical outcomes and biological characteristics, which may serve as potential biomarkers.

7.
Comput Biol Med ; 150: 106147, 2022 11.
Article in English | MEDLINE | ID: mdl-36201887

ABSTRACT

BACKGROUND: The recent development of artificial intelligence (AI) technologies coupled with medical imaging data has gained considerable attention, and offers a non-invasive approach for cancer diagnosis and prognosis. In this context, improved breast cancer (BC) molecular characteristics assessment models are foreseen to enable personalized strategies with better clinical outcomes compared to existing screening strategies. And it is a promising approach to developing models for hormone receptors (HR) and subtypes of BC patients from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data. METHODS: In this institutional review board-approved study, 174 BC patients with both DCE-MRI and RNA-seq data in the local database were analyzed. Slice images from tumor lesions and multi-scale peri-tumor regions were used as model inputs, and five representative pre-trained transfer learning (TF) networks, such as Inception-v3 and Xception, were employed to establish prediction models. A comprehensive analysis was performed using five-fold cross-validation to avoid overfitting, and accuracy (ACC) and area under the receiver operating characteristic curve (AUROC) to evaluate model performance. RESULTS: Xception achieved the superior results when using solely tumor regions, with highest AUROCs of 0.844 (95% CI: [0.841, 0.847]) and 0.784 (95% CI: [0.781, 0.788]) for estrogen receptor (ER) and progesterone receptor (PR), respectively, and best ACC of 0.467 (95% CI: [0.462, 0.470]) for PAM50 subtypes. A significant improvement in the model performance was observed when images of the peri-tumor region were included, with optimal results achieved using images of the tumor and the 10 mm peri-tumor regions. Xception-based TF models performed most effectively in predicting ER and PR statuses, with the AUROCs were 0.942 (95% CI: [0.940, 0.944]) and 0.920 (95% CI: [0.917, 0.922]), respectively, whereas for PAM50 subtypes, the Inception-v3-based network yielded the highest ACC as 0.742 (95% CI: [0.738, 0.746]). CONCLUSIONS: Transfer learning analysis based on DCE-MRI data of tumor and peri-tumor regions was helpful to the non-invasive assessment of molecular characteristics of BC.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Artificial Intelligence , Magnetic Resonance Imaging/methods , Machine Learning , Hormones
8.
Front Oncol ; 12: 943326, 2022.
Article in English | MEDLINE | ID: mdl-35965527

ABSTRACT

Background: To investigate reliable associations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) features and gene expression characteristics in breast cancer (BC) and to develop and validate classifiers for predicting PAM50 subtypes and prognosis from DCE-MRI non-invasively. Methods: Two radiogenomics cohorts with paired DCE-MRI and RNA-sequencing (RNA-seq) data were collected from local and public databases and divided into discovery (n = 174) and validation cohorts (n = 72). Six external datasets (n = 1,443) were used for prognostic validation. Spatial-temporal features of DCE-MRI were extracted, normalized properly, and associated with gene expression to identify the imaging features that can indicate subtypes and prognosis. Results: Expression of genes including RBP4, MYBL2, and LINC00993 correlated significantly with DCE-MRI features (q-value < 0.05). Importantly, genes in the cell cycle pathway exhibited a significant association with imaging features (p-value < 0.001). With eight imaging-associated genes (CHEK1, TTK, CDC45, BUB1B, PLK1, E2F1, CDC20, and CDC25A), we developed a radiogenomics prognostic signature that can distinguish BC outcomes in multiple datasets well. High expression of the signature indicated a poor prognosis (p-values < 0.01). Based on DCE-MRI features, we established classifiers to predict BC clinical receptors, PAM50 subtypes, and prognostic gene sets. The imaging-based machine learning classifiers performed well in the independent dataset (areas under the receiver operating characteristic curve (AUCs) of 0.8361, 0.809, 0.7742, and 0.7277 for estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2)-enriched, basal-like, and obtained radiogenomics signature). Furthermore, we developed a prognostic model directly using DCE-MRI features (p-value < 0.0001). Conclusions: Our results identified the DCE-MRI features that are robust and associated with the gene expression in BC and displayed the possibility of using the features to predict clinical receptors and PAM50 subtypes and to indicate BC prognosis.

9.
Genes (Basel) ; 14(1)2022 12 22.
Article in English | MEDLINE | ID: mdl-36672769

ABSTRACT

BACKGROUND: To investigate the relationship between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) radiomic features and the expression activity of hallmark pathways and to develop prediction models of pathway-level heterogeneity for breast cancer (BC) patients. METHODS: Two radiogenomic cohorts were analyzed (n = 246). Tumor regions were segmented semiautomatically, and 174 imaging features were extracted. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to identify significant imaging-pathway associations. Random forest regression was used to predict pathway enrichment scores. Five-fold cross-validation and grid search were used to determine the optimal preprocessing operation and hyperparameters. RESULTS: We identified 43 pathways, and 101 radiomic features were significantly related in the discovery cohort (p-value < 0.05). The imaging features of the tumor shape and mid-to-late post-contrast stages showed more transcriptional connections. Ten pathways relevant to functions such as cell cycle showed a high correlation with imaging in both cohorts. The prediction model for the mTORC1 signaling pathway achieved the best performance with the mean absolute errors (MAEs) of 27.29 and 28.61% in internal and external test sets, respectively. CONCLUSIONS: The DCE-MRI features were associated with hallmark activities and may improve individualized medicine for BC by noninvasively predicting pathway-level heterogeneity.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Contrast Media , Magnetic Resonance Imaging/methods
10.
Front Oncol ; 9: 985, 2019.
Article in English | MEDLINE | ID: mdl-31632916

ABSTRACT

Background: Breast cancer (BC) is a highly heterogeneous cancer. The interaction between immune system and BC is complex, widespread yet unclear. In this study, we aimed to reveal the heterogeneity of host systemic immune response to BC and understand the possible mechanisms that may drive the heterogeneity using transcriptomic data from peripheral blood mononuclear cells (PBMCs). Methods: Transcriptome-wide gene expressions of PBMCs in 33 BC patients were generated by RNA sequencing. An unsupervised clustering algorithm was employed to discover PBMC transcriptome subtypes among BC patients. Association analysis between PBMC subtypes and age, clinical stage, abundance of immune cells, and other clinical factors was performed to understand the underlying biological processes that may drive this heterogeneity. Immune gene signature identification and in silico survival analysis were performed to investigate the potential clinical implications of these PBMC subtypes. The findings were validated using the whole blood transcriptomes of an independent cohort. Results: We observed that established BC subtypes were not associated with PBMC gene expression profiles. Instead, we discovered and validated two new BC subtypes using PBMC transcriptome, which have distinct immune cell proportions, especially for lymphocytes (P = 5.22 × 10-12) and neutrophils (P = 1.13 × 10-14). Enrichment analysis of differentially expressed genes revealed that these two subtypes had distinct patterns of immune responses, including osteoclast differentiation and interleukin-10 signaling pathway. We developed two immune gene signatures that can differentiate these two BC PBMC subtypes. Further analysis suggested they had the ability to predict the clinical outcome of BC patients. Conclusions: PBMC transcriptome profiles can classify BC patients into two distinct subtypes. These two subtypes are mainly shaped by different immune cell abundance, which may have implications on clinical outcomes.

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