Using syncmers improves long-read mapping

As sequencing datasets keep growing larger, time and memory efficiency of read mapping are becoming more critical. Many clever algorithms and data structures were used to develop mapping tools for next generation sequencing, and in the last few years also for third generation long reads. A key idea in mapping algorithms is to sketch sequences with their minimizers. Recently, syncmers were introduced as an alternative sketching method that is more robust to mutations and sequencing errors. Here we introduce parameterized syncmer schemes, and provide a theoretical analysis for multi-parameter schemes. By combining these schemes with downsampling or minimizers we can achieve any desired compression and window guarantee. We introduced syncmer schemes into the popular minimap2 and Winnowmap2 mappers. In tests on simulated and real long read data from a variety of genomes, the syncmer-based algorithms reduced unmapped reads by 20-60% at high compression while using less memory. The advantage of syncmer-based mapping was even more pronounced at lower sequence identity. At sequence identity of 65-75% and medium compression, syncmer mappers had 50-60% fewer unmapped reads, and ∼ 10% fewer of the reads that did map were incorrectly mapped. We conclude that syncmer schemes improve mapping under higher error and mutation rates. This situation happens, for example, when the high error rate of long reads is compounded by a high mutation rate in a cancer tumor, or due to differences between strains of viruses or bacteria.

Construction of an exosome-functionalized graphene oxide based composite bionic smart drug delivery system and its anticancer activity

Graphene oxide has covalently modified by chito oligosaccharides and γ-polyglutamic acid to form GO-CO-γ-PGA, which exhibits excellent performance as a drug delivery carrier, but this carrier did not have the ability to actively target. In this study, the targeting property of breast cancer tumor cell exosomes was exploited to give GO-CO-γ-PGA the ability to target breast tumor cells (MDA-MB-231), and the drug mitoxantrone (MIT) was loaded to finally form EXO-GO-CO-γ-PGA-MIT with a loading capacity of 1.39 mg/mg. The pH response of EXO-GO-CO-γ-PGA showed a maximum cumulative release rate of 56.59% (pH 5.0) and 6.73% (pH 7.4) for MIT at different pH conditions. pH 7.4). In vitro cellular assays showed that EXO-GO-CO-γ-PGA-MIT was more potent in killing MDA-MB-231 cells due to its targeting ability and had a significantly higher pro-apoptotic capacity compared to GO-CO-γ-PGA-MIT. The results showed that this bionic nano-intelligent drug delivery system has good drug slow release function, can increase the local drug concentration of tumor and enhance the pro-apoptotic ability of MIT, so this newly synthesized bionic drug delivery carriers (EXO-GO-CO-γ-PGA-MIT) has potential application in breast cancer treatment.

Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states

Prostate cancer is the second most common malignancy in men worldwide and consists of a mixture of tumor and non-tumor cell types. To characterize the prostate cancer tumor microenvironment, we perform single-cell RNA-sequencing on prostate biopsies, prostatectomy specimens, and patient-derived organoids from localized prostate cancer patients. We uncover heterogeneous cellular states in prostate epithelial cells marked by high androgen signaling states that are enriched in prostate cancer and identify a population of tumor-associated club cells that may be associated with prostate carcinogenesis. ERG-negative tumor cells, compared to ERG-positive cells, demonstrate shared heterogeneity with surrounding luminal epithelial cells and appear to give rise to common tumor microenvironment responses. Finally, we show that prostate epithelial organoids harbor tumor-associated epithelial cell states and are enriched with distinct cell types and states from their parent tissues. Our results provide diagnostically relevant insights and advance our understanding of the cellular states associated with prostate carcinogenesis.

The Colorectal Cancer Tumor Microenvironment and Its Impact on Liver and Lung Metastasis

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related mortality worldwide. A total of 20% of CRC patients present with distant metastases, most frequently to the liver and lung. In the primary tumor, as well as at each metastatic site, the cellular components of the tumor microenvironment (TME) contribute to tumor engraftment and metastasis. These include immune cells (macrophages, neutrophils, T lymphocytes, and dendritic cells) and stromal cells (cancer-associated fibroblasts and endothelial cells). In this review, we highlight how the TME influences tumor progression and invasion at the primary site and its function in fostering metastatic niches in the liver and lungs. We also discuss emerging clinical strategies to target the CRC TME.

Novel Pathways for Targeting Tumor Angiogenesis in Metastatic Breast Cancer

Breast cancer is the most common cancer affecting women and is the second leading cause of cancer related death worldwide. Angiogenesis, the process of new blood vessel development from pre-existing vasculature, has been implicated in the growth, progression, and metastasis of cancer. Tumor angiogenesis has been explored as a key therapeutic target for decades, as the blockade of this process holds the potential to reduce the oxygen and nutrient supplies that are required for tumor growth. However, many existing anti-angiogenic approaches, such as those targeting Vascular Endothelial Growth Factor, Notch, and Angiopoietin signaling, have been associated with severe side-effects, limited survival advantage, and enhanced cancer regrowth rates. To address these setbacks, alternative pathways involved in the regulation of tumor angiogenesis are being explored, including those involving Bone Morphogenetic Protein-9 signaling, the Sonic Hedgehog pathway, Cyclooxygenase-2, p38-mitogen-activated protein kinase, and Chemokine Ligand 18. This review article will introduce the concept of tumor angiogenesis in the context of breast cancer, followed by an overview of current anti-angiogenic therapies, associated resistance mechanisms and novel therapeutic targets.

Classifying clinically actionable genetic mutations using KNN and SVM

Cancer is one of the major causes of death in humans. Early diagnosis of genetic mutations that cause cancer tumor growth leads to personalized medicine to the decease and can save the life of majority of patients. With this aim, Kaggle has conducted a competition to classify clinically actionable gene mutations based on clinical evidence and some other features related to gene mutations. The dataset contains 3321 training data points that can be classified into 9 classes. In this work, an attempt is made to classify these data points using K-nearest neighbors (KNN) and linear support vector machines (SVM) in a multi class environment. As the features are categorical, one hot encoding as well as response coding are applied to make them suitable to the classifiers. The prediction performance is evaluated using log loss and KNN has performed better with a log loss value of 1.10 compared to that of SVM 1.24.

BSA-Coated Gold Nanorods for NIR-II Photothermal Therapy

The second near infrared window is considered to be the optimal optical window for medical imaging and therapy as its capability of deep tissue penetration. The preparation of the gold nanorods with long wavelength absorption and low cytotoxicity is still a challenge. A series gold nanorods with large aspect ratio have been synthesized. Strong plasma absorption in the second near infrared window from 1000 to 1300 nm could be observed. The biocompatibility of the synthesized gold nanorods is dramatically improved via coating by bovine serum albumin (BSA), while the optical properties of which remains. The breast cancer tumor-bearing mouse could be well treated by the prepared gold nanorods with the NIR-II light intensity as low as 0.75 W/cm2. In summary, these results demonstrate the feasibility of using low illumination dose to treat tumor in the NIR-II region via the large aspect ratio gould nanoparticles.