Since cancer is a heterogeneous disease, tumor subtyping is crucial for improved treatment and prognosis. We have developed a subtype discovery tool, called PINSPlus, that is: (i) robust against ...noise and unstable quantitative assays, (ii) able to integrate multiple types of omics data in a single analysis and (iii) dramatically superior to established approaches in identifying known subtypes and novel subgroups with significant survival differences. Our validation on 12,158 samples from 44 datasets shows that PINSPlus vastly outperforms other approaches. The software is easy-to-use and can partition hundreds of patients in a few minutes on a personal computer.
The package is available at https://cran.r-project.org/package=PINSPlus. Data and R script used in this manuscript are available at https://bioinformatics.cse.unr.edu/software/PINSPlus/.
Supplementary data are available at Bioinformatics online.
Diamines are essential building blocks for the synthesis of agrochemicals, drugs, and organic materials, yet their synthesis remains challenging, as both nitrogens need to be differentiated and ...diverse substitution patterns (1,2, 1,3, or 1,4) are required. We report herein a new strategy giving access to 1,2, 1,3, and 1,4 amido azides as orthogonally protected diamines based on the nitrogen-directed diazidation of alkenes, cyclopropanes, and cyclobutanes. Commercially available copper thiophene-2-carboxylate (CuTc, 2 mol %) as catalyst promoted the diazidation of both π and σ C–C bonds within 10 min in the presence of readily available oxidants and trimethylsilyl azide. Selective substitution of the formed α-amino azide by carbon nucleophiles (electron-rich aromatic, malonate, organosilicon, organoboron, organozinc, and organomagnesium compounds) was then achieved in a one-pot fashion, leading to the formation of 1,2-, 1,3-, and 1,4-diamines with the amino groups protected orthogonally as an amide/carbamate and an azide.
We report the use of photocatalysis for the homolytic ring-opening of carbonyl cyclopropanes. In contrast to previous studies, our approach does not require a metal cocatalyst or a strong reductant. ...The carbonyl cyclopropanes can be employed for both 2σ + 2σ and 2σ + 2π annulation with either alkenes/alkynes or bicyclo1.1.0butanes, yielding cyclopent-anes/-enes and bicyclo3.1.1heptanes (BCHs), respectively. BCHs are promising bioisosteres for 1,2,4,5 tetra-substituted aromatic rings. Mechanistic studies, including density functional theory computation and a trapping experiment with DMPO, support a 1,3-biradical generated from cyclopropane as a key intermediate for these transformations.
Many high-throughput experiments compare two phenotypes such as disease vs. healthy, with the goal of understanding the underlying biological phenomena characterizing the given phenotype. Because of ...the importance of this type of analysis, more than 70 pathway analysis methods have been proposed so far. These can be categorized into two main categories: non-topology-based (non-TB) and topology-based (TB). Although some review papers discuss this topic from different aspects, there is no systematic, large-scale assessment of such methods. Furthermore, the majority of the pathway analysis approaches rely on the assumption of uniformity of p values under the null hypothesis, which is often not true.
This article presents the most comprehensive comparative study on pathway analysis methods available to date. We compare the actual performance of 13 widely used pathway analysis methods in over 1085 analyses. These comparisons were performed using 2601 samples from 75 human disease data sets and 121 samples from 11 knockout mouse data sets. In addition, we investigate the extent to which each method is biased under the null hypothesis. Together, these data and results constitute a reliable benchmark against which future pathway analysis methods could and should be tested.
Overall, the result shows that no method is perfect. In general, TB methods appear to perform better than non-TB methods. This is somewhat expected since the TB methods take into consideration the structure of the pathway which is meant to describe the underlying phenomena. We also discover that most, if not all, listed approaches are biased and can produce skewed results under the null.
Aminocyclopropanes are versatile building blocks for accessing high value-added nitrogen-containing products. To control ring-opening promoted by ring strain, the Lewis acid activation of ...donor–acceptor substituted systems is now well established. Over the last decade, alternative approaches have emerged proceeding via the formation of radical intermediates, alleviating the need for double activation of the cyclopropanes. This tutorial review summarizes key concepts and recent progress in ring-opening transformations of aminocyclopropanes via radical intermediates, divided into formal cycloadditions and 1,3-difunctionalizations.
Advances in high-throughput technologies allow for measurements of many types of omics data, yet the meaningful integration of several different data types remains a significant challenge. Another ...important and difficult problem is the discovery of molecular disease subtypes characterized by relevant clinical differences, such as survival. Here we present a novel approach, called
erturbation clustering for data
tegration and disease
ubtyping (PINS), which is able to address both challenges. The framework has been validated on thousands of cancer samples, using gene expression, DNA methylation, noncoding microRNA, and copy number variation data available from the Gene Expression Omnibus, the Broad Institute, The Cancer Genome Atlas (TCGA), and the European Genome-Phenome Archive. This simultaneous subtyping approach accurately identifies known cancer subtypes and novel subgroups of patients with significantly different survival profiles. The results were obtained from genome-scale molecular data without any other type of prior knowledge. The approach is sufficiently general to replace existing unsupervised clustering approaches outside the scope of bio-medical research, with the additional ability to integrate multiple types of data.
We report the first oxidative C-H alkynylation of arylcyclopropanes. Irradiation of ethynylbenziodoxolone (EBX) reagents with visible light at 440 nm promoted the reaction. By the choice of the aryl ...group on the cyclopropane, it was possible to completely switch the outcome of the reaction from the alkynylation of the C-H bond to the oxyalkynylation of the C-C bond, which proceeded without the need for a catalyst, in contrast to previous works. The oxyalkynylation could also be extended to aminocyclopropanes as well as styrenes. Computations indicated that the C-H activation became a favoured nearly barrierless process in the presence of two
ortho
methyl groups on the benzene ring.
C-C or C-H alkynylation of aryl cyclopropanes was realized by direct activation of EBX reagents with visible light. With
ortho
methyl groups on the benzene, C-H functionalization became favoured.
Gene regulatory network is a complicated set of interactions between genetic materials, which dictates how cells develop in living organisms and react to their surrounding environment. Robust ...comprehension of these interactions would help explain how cells function as well as predict their reactions to external factors. This knowledge can benefit both developmental biology and clinical research such as drug development or epidemiology research. Recently, the rapid advance of single-cell sequencing technologies, which pushed the limit of transcriptomic profiling to the individual cell level, opens up an entirely new area for regulatory network research. To exploit this new abundant source of data and take advantage of data in single-cell resolution, a number of computational methods have been proposed to uncover the interactions hidden by the averaging process in standard bulk sequencing. In this article, we review 15 such network inference methods developed for single-cell data. We discuss their underlying assumptions, inference techniques, usability, and pros and cons. In an extensive analysis using simulation, we also assess the methods' performance, sensitivity to dropout and time complexity. The main objective of this survey is to assist not only life scientists in selecting suitable methods for their data and analysis purposes but also computational scientists in developing new methods by highlighting outstanding challenges in the field that remain to be addressed in the future development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Microalgae:activated sludge ratio (3:1) was the optimum co-culture operation.•Microalgae played a vital role in biomass production and nutrient removal.•Under the optimum ratio, COD ...removal was obtained 98% in 4 days.•Biological assimilation majorly contributed to nutrient removal in the co-culture PBR.
In this study, mixed culture (microalgae:activated sludge) of a photobioreactor (PBR) were investigated at different inoculation ratios (1:0, 9:1, 3:1, 1:1, 0:1 wt/wt). This work was not only to determine the optimal ratio for pollutant remediation and biomass production but also to explore the role of microorganisms in the co-culture system. The results showed high total biomass concentrations were obtained from 1:0 and 3:1 ratio being values of 1.06, 1.12 g L-1, respectively. Microalgae played a dominant role in nitrogen removal via biological assimilation while activated sludge was responsible for improving COD removal. Compared with the single culture of microalgae, the symbiosis between microalgae and bacteria occurred at 3:1 and 1:1 ratio facilitated a higher COD removal by 37.5–45.7 %. In general, combined assessment based on treatment performance and biomass productivity facilitated to select an optimal ratio of 3:1 for the operation of the co-culture PBR.
Urine has been considered as an ideal nutrient source for microalgae cultivation thanks to its composition containing the high concentrations of nitrogen and phosphorus. Herein, the microalgae growth ...in urine was evaluated in a lab-scale membrane photobioreactor (MPBR) system. This work aimed to validate the influence of low biomass retention times (BRT) (10, 7, 5, 3, 2 d) on nutrient remediation and biomass productivity. It revealed that BRT of 7 d resulted in synergistically high biomass production (biomass productivity of 313 mg/L.d) and removal rates (TN of 90.5 mg/L.d and TP of 4.7 mg/L.d). Notably, the short BRT of 2–5 d was not sufficient to trigger actively growing microalgae and thus reduced biomass production rate. In addition, as operated at a low flux of 2 L/m2.h, MPBR system required no physical cleaning for 100 days of operation. The BRT-dependent biomass concentration played a pivotal role in changing the fouling rate of MPBR; however, the fouling is reversible in the MPBR system under the low flux condition.
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•A membrane photobioreactor was applied for nutrient capture from urine.•Urine was indeed a potential source for microalgae biomass production.•Biomass retention time (BRT) of 7 d was proposed for optimum operation.•Under BRT of 2–5 d, such a drastic decrease in biomass accumulation was noticed.•The BRT-dependent biomass accumulation governed the TN removal rate.
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