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Methods Mol Biol 2021 ;2284:331-342

Department of Applied Mathematics, Yale University, New Haven, CT, USA.

Dimensionality reduction is a crucial step in essentially every single-cell RNA-sequencing (scRNA-seq) analysis. In this chapter, we describe the typical dimensionality reduction workflow that is used for scRNA-seq datasets, specifically highlighting the roles of principal component analysis, t-distributed stochastic neighborhood embedding, and uniform manifold approximation and projection in this setting. We particularly emphasize efficient computation; the software implementations used in this chapter can scale to datasets with millions of cells. Read More

Front Genet 2021 23;12:646936. Epub 2021 Mar 23.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Single-cell RNA sequencing (scRNA-seq) is a high-throughput sequencing technology performed at the level of an individual cell, which can have a potential to understand cellular heterogeneity. However, scRNA-seq data are high-dimensional, noisy, and sparse data. Dimension reduction is an important step in downstream analysis of scRNA-seq. Read More

Rev Sci Instrum 2021 Mar;92(3):033201

Sensor Science Division, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA.

We create a pair of symmetric Bitter-type electromagnet assemblies capable of producing multiple field configurations including uniform magnetic fields, spherical quadruple traps, or Ioffe-Pritchard magnetic bottles. Unlike other designs, our coil allows both radial and azimuthal cooling water flows by incorporating an innovative 3D-printed water distribution manifold. Combined with a double-coil geometry, such orthogonal flows permit stacking of non-concentric Bitter coils. Read More

Comput Struct Biotechnol J 2021 7;19:1497-1511. Epub 2021 Mar 7.

Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, 38010 Santa Cruz de Tenerife, Spain.

Since its introduction, nanopore sequencing has enhanced our ability to study complex microbial samples through the possibility to sequence long reads in real time using inexpensive and portable technologies. The use of long reads has allowed to address several previously unsolved issues in the field, such as the resolution of complex genomic structures, and facilitated the access to metagenome assembled genomes (MAGs). Furthermore, the low cost and portability of platforms together with the development of rapid protocols and analysis pipelines have featured nanopore technology as an attractive and ever-growing tool for real-time in-field sequencing for environmental microbial analysis. Read More

Cancer Metab 2021 Mar 24;9(1):13. Epub 2021 Mar 24.

Department of Orthopaedic Surgery, Duke University, 311 Trent, Durham, NC, 27710, USA.

Background: Majority of chondrosarcomas are associated with a number of genetic alterations, including somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 genes, but the downstream effects of these mutated enzymes on cellular metabolism and tumor energetics are unknown. As IDH mutations are likely to be involved in malignant transformation of chondrosarcomas, we aimed to exploit metabolomic changes in IDH mutant and non-mutant chondrosarcomas.

Methods: Here, we profiled over 69 metabolites in 17 patient-derived xenografts by targeted mass spectrometry to determine if metabolomic differences exist in mutant IDH1, mutant IDH2, and non-mutant chondrosarcomas. Read More

Front Artif Intell 2020 30;3:564878. Epub 2020 Nov 30.

Department of Applied Geomatics, Université de Sherbrooke, Sherbrooke, QC, Canada.

(FD) is a grapevine disease caused by phytoplasmas and transmitted by leafhoppers that has been spreading in European vineyards despite significant efforts to control it. In this study, we aim to develop a model for the automatic detection of FD-like symptoms (which encompass other grapevine yellows symptoms). The concept is to detect likely FD-affected grapevines so that samples can be removed for FD laboratory identification, followed by uprooting if they test positive, all to be conducted quickly and without omission, thus avoiding further contamination in the fields. Read More

Cancers (Basel) 2021 Feb 12;13(4). Epub 2021 Feb 12.

Department of Molecular Carcinogenesis, Medical University of Lodz, 90-752 Lodz, Poland.

Notch signaling is an evolutionarily conserved pathway regulating normal embryonic development and homeostasis in a wide variety of tissues. It is also critically involved in carcinogenesis, as well as cancer progression. Activation of the Notch pathway members can be either oncogenic or suppressive, depending on tissue context. Read More

Mol Ther Methods Clin Dev 2021 Mar 26;20:601-614. Epub 2021 Jan 26.

Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), PO Box 34110, Doha 00000, Qatar.

Triple-negative breast cancer (TNBC) patients exhibit variable responses to chemotherapy, suggesting an underlying molecular heterogeneity. In the current study, we analyzed publicly available transcriptome data from 360 TNBC and 88 normal breast tissues, which revealed activation of nucleosome and cell cycle as the hallmarks of TNBC. Mechanistic network analysis identified activation of FOXM1 and ERBB2, and suppression of TP53 and NURP1 networks in TNBC. Read More

Toxicol Pathol 2021 Mar 3:192623321993425. Epub 2021 Mar 3.

Novartis Institutes for BioMedical Research, Basel, Switzerland.

We introduce HistoNet, a deep neural network trained on normal tissue. On 1690 slides with rat tissue samples from 6 preclinical toxicology studies, tissue regions were outlined and annotated by pathologists into 46 different tissue classes. From these annotated regions, we sampled small 224 × 224 pixels images (patches) at 6 different levels of magnification. Read More

Comput Biol Med 2021 04 22;131:104264. Epub 2021 Feb 22.

Department of Mathematics, Michigan State University, MI, 48824, USA; Department of Electrical and Computer Engineering, Michigan State University, MI, 48824, USA; Department of Biochemistry and Molecular Biology, Michigan State University, MI, 48824, USA. Electronic address:

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a worldwide devastating effect. Understanding the evolution and transmission of SARS-CoV-2 is of paramount importance for controlling, combating and preventing COVID-19. Due to the rapid growth in both the number of SARS-CoV-2 genome sequences and the number of unique mutations, the phylogenetic analysis of SARS-CoV-2 genome isolates faces an emergent large-data challenge. Read More

Spectrochim Acta A Mol Biomol Spectrosc 2021 May 4;252:119547. Epub 2021 Feb 4.

Northwestern University / Art Institute of Chicago Center for Scientific Studies in the Arts (NU-ACCESS), 2145 Sheridan Road, Evanston, IL, United States. Electronic address:

This study assesses the potential of Uniform Manifold Approximation and Projection (UMAP) as an alternative tool to t-distributed Stochastic Neighbor Embedding (t-SNE) for the reduction and visualization of visible spectral images of works of art. We investigate the influence of UMAP parameters-such as, correlation distance, minimum embedding distance, as well as number of embedding neighbors- on the reduction and visualization of spectral images collected from Poèmes Barbares (1896), a major work by the French artist Paul Gauguin in the collection of the Harvard Art Museums. The use of a cosine distance metric and number of neighbors equal to 10 preserves both the local and global structure of the Gauguin dataset in a reduced two-dimensional embedding space thus yielding simple and clear groupings of the pigments used by the artist. Read More

Sensors (Basel) 2021 Feb 8;21(4). Epub 2021 Feb 8.

Electrical Engineering Unit, Faculty of Information Technology and Communication Sciences, Tampere University, 33720 Tampere, Finland.

The 5G network is considered as the essential underpinning infrastructure of manned and unmanned autonomous machines, such as drones and vehicles. Besides aiming to achieve reliable and low-latency wireless connectivity, positioning is another function provided by the 5G network to support the autonomous machines as the coexistence with the Global Navigation Satellite System (GNSS) is typically supported on smart 5G devices. This paper is a pilot study of using 5G uplink physical layer channel sounding reference signals (SRSs) for 3D user equipment (UE) positioning. Read More

Brief Bioinform 2021 Feb 3. Epub 2021 Feb 3.

School of Electronic and Communication Engineering, Shenzhen Polytechnic.

Anticancer peptides constitute one of the most promising therapeutic agents for combating common human cancers. Using wet experiments to verify whether a peptide displays anticancer characteristics is time-consuming and costly. Hence, in this study, we proposed a computational method named identify anticancer peptides via deep representation learning features (iACP-DRLF) using light gradient boosting machine algorithm and deep representation learning features. Read More

Cell Death Discov 2021 Jan 25;7(1):23. Epub 2021 Jan 25.

College of Health & Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar.

Cumulative evidence suggests added benefit for neoadjuvant chemotherapy (NAC) in a subset of triple-negative breast cancer (TNBC) patients. Herein we identified the long noncoding RNA (lncRNA) transcriptional landscape associated with TNBC resistance to NAC, employing 1758 single cells from three extinction and three persistence TNBC patients. Using Iterative Clustering and Guide-gene Selection (ICGS) and uniform manifold approximation and projection (UMAP) dimensionality reduction analysis, we observed single cells derived from each patient to largely cluster together. Read More

Interdiscip Sci 2021 Mar 21;13(1):83-90. Epub 2021 Jan 21.

College of Mathematics and System Sciences, Xinjiang University, Urumqi, China.

Clustering is a common method to identify cell types in single cell analysis, but the increasing size of scRNA-seq datasets brings challenges to single cell clustering. Therefore, it is an urgent need to design a faster and more accurate clustering method for large-scale scRNA-seq data. In this paper, we proposed a new method for single cell clustering. Read More

Nat Biotechnol 2021 Jan 18. Epub 2021 Jan 18.

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Nonlinear data visualization methods, such as t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP), summarize the complex transcriptomic landscape of single cells in two dimensions or three dimensions, but they neglect the local density of data points in the original space, often resulting in misleading visualizations where densely populated subsets of cells are given more visual space than warranted by their transcriptional diversity in the dataset. Here we present den-SNE and densMAP, which are density-preserving visualization tools based on t-SNE and UMAP, respectively, and demonstrate their ability to accurately incorporate information about transcriptomic variability into the visual interpretation of single-cell RNA sequencing data. Applied to recently published datasets, our methods reveal significant changes in transcriptomic variability in a range of biological processes, including heterogeneity in transcriptomic variability of immune cells in blood and tumor, human immune cell specialization and the developmental trajectory of Caenorhabditis elegans. Read More

ArXiv 2020 Dec 30. Epub 2020 Dec 30.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a worldwide devastating effect. The understanding of evolution and transmission of SARS-CoV-2 is of paramount importance for the COVID-19 control, combating, and prevention. Due to the rapid growth of both the number of SARS-CoV-2 genome sequences and the number of unique mutations, the phylogenetic analysis of SARS-CoV-2 genome isolates faces an emergent large-data challenge. Read More

Front Cell Dev Biol 2020 15;8:592616. Epub 2020 Dec 15.

Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland.

The Notch pathway involves evolutionarily conserved signaling regulating the development of the female tract organs such as breast, ovary, cervix, and uterine endometrium. A great number of studies revealed Notch aberrancies in association with their carcinogenesis and disease progression, the management of which is still challenging. The present study is a comprehensive review of the available literature on Notch signaling during the normal development and carcinogenesis of the female tract organs. Read More

Anal Chem 2021 01 29;93(3):1677-1685. Epub 2020 Dec 29.

Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, Moscow 121205, Russian Federation.

Mass spectrometry imaging (MSI) has become an important tool for 2D profiling of biological tissues, allowing for the visualization of individual compound distributions in the sample. Based on this information, it is possible to investigate the molecular organization within any particular tissue and detect abnormal regions (such as tumor regions) and many other biologically relevant phenomena. However, the large number of compounds present in the spectra hinders the productive analysis of large MSI datasets when utilizing standard tools. Read More

IEEE Trans Neural Netw Learn Syst 2020 Dec 24;PP. Epub 2020 Dec 24.

The performance of graph-based feature selection methods relies heavily on the quality of the construction of the similarity matrix. However, most of the graphs on these methods are initially fixed, where few of them are constrained. Once the graph is determined, it will remain constant in the whole optimization process. Read More

Am J Physiol Gastrointest Liver Physiol 2021 03 23;320(3):G396-G410. Epub 2020 Dec 23.

University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

Poor translatability of animal disease models has hampered the development of new inflammatory bowel disorder (IBD) therapeutics. We describe a preclinical, ex vivo system using freshly obtained and well-characterized human colorectal tissue from patients with ulcerative colitis (UC) and healthy control (HC) participants to test potential therapeutics for efficacy and target engagement, using the JAK/STAT inhibitor tofacitinib (TOFA) as a model therapeutic. Colorectal biopsies from HC participants and patients with UC were cultured and stimulated with multiple mitogens ± TOFA. Read More

Metabolites 2020 Dec 18;10(12). Epub 2020 Dec 18.

Kolver Diabetes Center and Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.

Obesity is closely associated with adipose tissue inflammation and insulin resistance. Dysglycemia and type 2 diabetes results when islet β cells fail to maintain appropriate insulin secretion in the face of insulin resistance. To clarify the early transcriptional events leading to β-cell failure in the setting of obesity, we fed male C57BL/6J mice an obesogenic, high-fat diet (60% kcal from fat) or a control diet (10% kcal from fat) for one week, and islets from these mice (from four high-fat- and three control-fed mice) were subjected to single-cell RNA sequencing (sc-RNAseq) analysis. Read More

J Chem Phys 2020 Dec;153(22):224106

Institute of Physics, University of Szczecin, Wielkopolska 15, 70-451 Szczecin, Poland.

An efficient computational scheme for the calculation of highly accurate ground-state electronic properties of the helium isoelectronic series, permitting uniform description of its members down to the critical nuclear charge Z, is described. It is based upon explicitly correlated basis functions derived from the regularized Krylov sequences (which constitute the core of the free iterative CI/free complement method of Nakatsuji) involving a term that introduces split length scales. For the nuclear charge Z approaching Z, the inclusion of this term greatly reduces the error in the variational estimate for the ground-state energy, restores the correct large-r asymptotics of the one-electron density ρ(Z; r), and dramatically alters the manifold of the pertinent natural amplitudes and natural orbitals. Read More

Ann Transl Med 2020 Nov;8(21):1467

Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland.

Lung emphysema represents a major public health burden and still accounts for five percent of all deaths worldwide. Hence, it is essential to further understand this disease in order to develop effective diagnostic and therapeutic strategies. Lung emphysema is an irreversible enlargement of the airways distal to the terminal bronchi (i. Read More

Cells 2020 12 8;9(12). Epub 2020 Dec 8.

Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands.

The flow cytometric detection of intracellular (IC) signaling proteins and transcription factors (TFs) will help to elucidate the regulation of B cell survival, proliferation and differentiation. However, the simultaneous detection of signaling proteins or TFs with membrane markers (MMs) can be challenging, as the required fixation and permeabilization procedures can affect the functionality of conjugated antibodies. Here, a phosphoflow method is presented for the detection of activated NF-κB p65 and phosphorylated STAT1, STAT3, STAT5 and STAT6, together with the B cell differentiation MMs CD19, CD27 and CD38. Read More

Talanta 2021 Feb 15;223(Pt 2):121665. Epub 2020 Sep 15.

Department of Chemistry, Wake Forest University, Salem Hall, Box 7486, Winston-Salem, NC, 27109, USA. Electronic address:

Supervised and unsupervised machine learning methods are used to evaluate matrix effects caused by carbon and easily ionizable elements (EIEs) on analytical signals of inductively coupled plasma optical emission spectrometry (ICP OES). A simple experimental approach was used to produce a series of synthetic solutions with varying levels of matrix complexity. Analytical lines (n = 29), with total line energies (E) in the 5. Read More

Entropy (Basel) 2020 Apr 20;22(4). Epub 2020 Apr 20.

School of Mathematics and Statistics, Carlton University, Ottawa, ON K1S 5B6, Canada.

When using Bayesian inference, one needs to choose a prior distribution for parameters. The well-known Jeffreys prior is based on the Riemann metric tensor on a statistical manifold. Takeuchi and Amari defined the α -parallel prior, which generalized the Jeffreys prior by exploiting a higher-order geometric object, known as a Chentsov-Amari tensor. Read More

Vaccines (Basel) 2020 Dec 2;8(4). Epub 2020 Dec 2.

IRMB, University Montpellier, INSERM, 34295 Montpellier, France.

The lymphocyte lineage natural killer (NK) cell is part of the innate immune system and protects against pathogens and tumor cells. NK cells are the main cell effectors of the monoclonal antibodies (mAbs) that mediates antibody-dependent cell cytotoxicity (ADCC). Hence, it is relevant to understand NK physiology and status to investigate the biological effect of mAbs in the clinic. Read More

J Neurosci Res 2021 Mar 16;99(3):731-749. Epub 2020 Nov 16.

Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA.

The cornea is the most innervated tissue in the human body. Myelinated axons upon inserting into the peripheral corneal stroma lose their myelin sheaths and continue into the central cornea wrapped by only nonmyelinating corneal Schwann cells (nm-cSCs). This anatomical organization is believed to be important for central vision. Read More

Cells 2020 10 29;9(11). Epub 2020 Oct 29.

College of Health & Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), PO Box 34110, Doha, Qatar.

Cumulative data link cytokine storms with coronavirus disease 2019 (COVID-19) severity. The precise identification of immune cell subsets in bronchoalveolar lavage (BAL) and their correlation with COVID-19 disease severity are currently being unraveled. Herein, we employed iterative clustering and guide-gene selection 2 (ICGS2) as well as uniform manifold approximation and projection (UMAP) dimensionality reduction computational algorithms to decipher the complex immune and cellular composition of BAL, using publicly available datasets from a total of 68,873 single cells derived from two healthy subjects, three patients with mild COVID-19, and five patients with severe COVID-19. Read More