抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

Pattern Recognition and Machine Learning

In a previous paper, we introduced MUSCLE, a new program for creating multiple alignments of protein sequences, giving a brief summary of the algorithm and showing MUSCLE to achieve the highest scores reported to date on four alignment accuracy benchmarks. Here we present a more complete discussion of the algorithm, describing several previously unpublished techniques that improve biological accuracy and / or computational complexity. We introduce a new option, MUSCLE-fast, designed for high-throughput applications. We also describe a new protocol for evaluating objective functions that align two profiles. We compare the speed and accuracy of MUSCLE with CLUSTALW, Progressive POA and the MAFFT script FFTNS1, the fastest previously published program known to the author. Accuracy is measured using four benchmarks: BAliBASE, PREFAB, SABmark and SMART. We test three variants that offer highest accuracy (MUSCLE with default settings), highest speed (MUSCLE-fast), and a carefully chosen compromise between the two (MUSCLE-prog). We find MUSCLE-fast to be the fastest algorithm on all test sets, achieving average alignment accuracy similar to CLUSTALW in times that are typically two to three orders of magnitude less. MUSCLE-fast is able to align 1,000 sequences of average length 282 in 21 seconds on a current desktop computer. MUSCLE offers a range of options that provide improved speed and / or alignment accuracy compared with currently available programs. MUSCLE is freely available at http://www.drive5.com/muscle
 .

/pdf/muscle-a-multiple-sequence-alignment-method-with-reduced-9d0g1qzdlk.pdf

MUSCLE: a multiple sequence alignment method with reduced time and space complexity

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

Inhibition of anaerobic digestion process: A review

Motivation: Genetic recombination and, in particular, genetic shuffling are at odds with sequence comparison by alignment, which assumes conservation of contiguity between homologous segments. A variety of theoretical foundations are being used to derive alignment-free methods that overcome this limitation. The formulation of alternative metrics for dissimilarity between sequences and their algorithmic implementations are reviewed. Results: The overwhelming majority of work on alignmentfree sequence has taken place in the past two decades, with most reports published in the past 5 years. Two main categories of methods have been proposed—methods based on word (oligomer) frequency, and methods that do not require resolving the sequence with fixed word length segments. The first category is based on the statistics of word frequency, on the distances defined in a Cartesian space defined by the frequency vectors, and on the information content of frequency distribution. The second category includes the use of Kolmogorov complexity and Chaos Theory. Despite their low visibility, alignment-free metrics are in fact already widely used as pre-selection filters for alignment-based querying of large applications. Recent work is furthering their usage as a scale-independent methodology that is capable of recognizing homology when loss of contiguity is beyond the possibility of alignment. Availability: Most of the alignment-free algorithms reviewed were implemented in MATLAB code and are available at http://bioinformatics.musc.edu/resources.html. Contact: almeidaj@musc.edu; svinga@itqb.unl.pt

/pdf/alignment-free-sequence-comparison-a-review-13eerno6qs.pdf

Alignment-free sequence comparison-a review.

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. The strength of these methods makes them particularly useful for next-generation sequencing data processing and analysis. However, many researchers are unclear about how these methods work, how they compare to alignment-based methods, and what their potential is for use for their research. We address these questions and provide a guide to the currently available alignment-free sequence analysis tools.

https://link.springer.com/content/pdf/10.1186%2Fs13059-017-1319-7.pdf

Alignment-free sequence comparison: benefits, applications, and tools

A culture of sulfate reducing bacteria (SRB) growing on lactate and sulfate was incubated at different pH values in the range of 5.8-7.0. The effect of pH on growth rate was determined in this pH range; the highest growth rate was observed at pH 6.7. Hydrogen sulfide produced from sulfate reduction was found to have a direct and reversible toxicity effect on the SRB. A hydrogen sulfide Concentration of 547 mg/L (16.1 mM) completely inhibited the culture growth. Comparison between acetic acid and hydrogen sulfide inhibition is presented and the concomitant inhibition kinetics are mathematically described.

Effect of hydrogen sulfide on growth of sulfate reducing bacteria.

Furfural was reduced to furfuryl alcohol by Saccaromyces cerevisiae with a yield of 0.97 +/- 0.01 mmol/ mmol causing a lag phase in cell growth. In the presence of 29 mM, furfural the cell-mass yield on glucose decreased from 11.0 +/- 0.1 mg/mmol (0.06 +/- 0.0006 g/g) in a reference fermentation without furfural to 9.7 +/- 0.07 mg/ mmol (0.05 +/- 0.0004 g/g), whereas the ethanol yield on glucose increased from 1.6 +/- 0.03 to 1.7 +/- 0.03 mmol/mmol. No glycerol was excreted during furfural reduction, and the lag phase in acetate production was extended from 1 h in the reference fermentation to 5 h in the presence of furfural. Acetaldehyde and pyruvate were excreted during the furfural reduction phase. Cell growth and cell maintenance were proportional to glucose consumption during the entire fermentation, whereas the cell-mass yield on ATP produced was low during furfural reduction. These observations indicate that furfural addition to a batch culture decreased cell replication without inhibiting cell activity (designated as replicative inactivation). The absence of glycerol production during furfural reduction suggests that furfural acted as an alternative redox sink oxidizing excess NADH formed in biosynthesis. A mechanistic mathematical model was developed that described accurately the fermentation in the absence and presence of furfural. The model was based on the assumptions that: (i) furfural reduction to furfuryl alcohol by NADH-dependent dehydrogenases had a higher priority than reduction of dihydroxyacetone phosphate to glycerol; and (ii) furfural caused inactivation of cell replication. The effect of furfural on cell replication is discussed in relation to acetaldehyde formation. Inactivation of cell replication was modeled by considering two populations within the cell culture, both metabolically active, but only one replicating. The kinetic description was developed as a tool to estimate transient fluxes of carbon, NADH/NAD+ and ATP/ADP.

Influence of Furfural on anaerobic glycolytic kinetics of Saccharomyces cerevisiae in batch culture

Rationale: Modern molecular biology is generating data of unprecedented quantity and quality. Particularly exciting for biochemical pathway modeling and proteomics are comprehensive, time-dense profiles of metabolites or proteins that are measurable, for instance, with mass spectrometry, nuclear magnetic resonance or protein kinase phosphorylation. These profiles contain a wealth of information about the structure and dynamics of the pathway or network from which the data were obtained. The retrieval of this information requires a combination of computational methods and mathematical models, which are typically represented as systems of ordinary differential equations.

Results: We show that, for the purpose of structure identification, the substitution of differentials with estimated slopes in non-linear network models reduces the coupled system of differential equations to several sets of decoupled algebraic equations, which can be processed efficiently in parallel or sequentially. The estimation of slopes for each time series of the metabolic or proteomic profile is accomplished with a 'universal function' that is computed directly from the data by cross-validated training of an artificial neural network (ANN).

Conclusions: Without preprocessing, the inverse problem of determining structure from metabolic or proteomic profile data is challenging and computationally expensive. The combination of system decoupling and data fitting with universal functions simplifies this inverse problem very significantly. Examples show successful estimations and current limitations of the method.

Availability: A preliminary Web-based application for ANN smoothing is accessible at http://bioinformatics.musc.edu/webmetabol/. S-systems can be interactively analyzed with the user-friendly freeware PLAS© (http://correio.cc.fc.ul.pt/~aenf/plas.html) or with the MATLAB module BSTLab (http://bioinformatics.musc.edu/bstlab/), which is currently being beta-tested.

Jonas S. Almeida

Papers

Alignment-free sequence comparison-a review.

Alignment-free sequence comparison: benefits, applications, and tools

Effect of hydrogen sulfide on growth of sulfate reducing bacteria.

Influence of Furfural on anaerobic glycolytic kinetics of Saccharomyces cerevisiae in batch culture

Decoupling dynamical systems for pathway identification from metabolic profiles