ePat: extended PROVEAN annotation tool

The 'ePat' (extended PROVEAN annotation tool) is a software tool that extends the functionality of PROVEAN: a software tool for predicting whether amino acid substitutions and indels will affect the biological function of proteins. The 'ePat' extends the conventional PROVEAN to enable the following two things. First is to calculate the pathogenicity of indel mutations with frameshift and variants near splice junctions, for which the conventional PROVEAN could not calculate the pathogenicity of these variants. Second is to use batch processing to calculate the pathogenicity of multiple variants in a variants list (VCF file) in a single step. In order to identify variants that are predicted to be functionally important from the variants list, ePat can help filter out variants that affect biological functions by utilizing not only point mutations, and indel mutations that does not cause frameshift, but also frameshift, stop gain, and splice variants.

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Mechanism of Metronidazole Resistance inHelicobacter pylori: Comparison of the rdxA Gene Sequences in 30 Strains

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.8.2207-2210.2000 ◽

2000 ◽

Vol 44 (8) ◽

pp. 2207-2210 ◽

Cited By ~ 26

Author(s):

Nadia Maggi Solcà ◽

Marco Valerio Bernasconi ◽

Jean-Claude Piffaretti

Keyword(s):

Phylogenetic Analysis ◽

Helicobacter Pylori ◽

Amino Acid ◽

Resistant Strain ◽

Point Mutations ◽

Housekeeping Genes ◽

Amino Acid Substitutions ◽

Metronidazole Resistance ◽

Nucleotide Mutation ◽

Nucleotide Insertion

ABSTRACT The rdxA gene of 30 independently isolatedHelicobacter pylori strains was sequenced. A comparison of the rdxA sequences revealed a higher percentage of amino acid substitutions in the corresponding protein than in other housekeeping genes. Out of 122 point mutations, 41 were missense and 4 were nonsense. A resistant strain with a nucleotide insertion in therdxA sequence was also found. With the exception of the point mutations and the insertion generating a stop signal, no particular nucleotide mutation or amino acid substitution could be associated to metronidazole resistance. Moreover, phylogenetic analysis of the 30 nucleotide sequences did not demonstrate specific clusters associated with the resistance phenotype.

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Identification of separate domains in the adenovirus E1A gene for immortalization activity and the activation of virus early genes.

Molecular and Cellular Biology ◽

10.1128/mcb.6.10.3470 ◽

1986 ◽

Vol 6 (10) ◽

pp. 3470-3480 ◽

Cited By ~ 98

Author(s):

E Moran ◽

B Zerler ◽

T M Harrison ◽

M B Mathews

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Point Mutations ◽

Apparent Molecular Weight ◽

Amino Acid Position ◽

Cysteine Residue ◽

Transformation Function ◽

Single Amino Acid ◽

Amino Acid Substitutions ◽

E1a Gene

The transformation and early adenovirus gene transactivation functions of the E1A region were analyzed with deletion and point mutations. Deletion of amino acids from position 86 through 120 had little effect on the lytic or transforming functions of the E1A products, while deletion of amino acids from position 121 through 150 significantly impaired both functions. The sensitivity of the transformation function to alterations in the region from amino acid position 121 to 150 was further indicated by the impairment of transforming activity resulting from single amino acid substitutions at positions 124 and 135. Interestingly, conversion of a cysteine residue at position 124 to glycine severely impaired the transformation function without affecting the early adenovirus gene activating functions. Single amino acid substitutions in a different region of the E1A gene had the converse effect. All the mutants produced polypeptides of sufficient stability to be detected by Western immunoblot analysis. The single amino acid substitutions at positions 124 and 135, although impairing the transformation functions, did not detectably alter the formation of the higher-apparent-molecular-weight forms of the E1A products.

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Mumame: a software tool for quantifying gene-specific point-mutations in shotgun metagenomic data

Metabarcoding and Metagenomics ◽

10.3897/mbmg.3.36236 ◽

2019 ◽

Vol 3 ◽

Cited By ~ 1

Author(s):

Shruthi Magesh ◽

Viktor Jonsson ◽

Johan Bengtsson-Palme

Keyword(s):

Microbial Communities ◽

Point Mutations ◽

Software Tool ◽

Metagenomic Data ◽

Data Sets ◽

Resistance Mutations ◽

Shotgun Metagenomics ◽

Key Factor ◽

Detection Of Mutations ◽

And Function

Metagenomics has emerged as a central technique for studying the structure and function of microbial communities. Often the functional analysis is restricted to classification into broad functional categories. However, important phenotypic differences, such as resistance to antibiotics, are often the result of just one or a few point mutations in otherwise identical sequences. Bioinformatic methods for metagenomic analysis have generally been poor at accounting for this fact, resulting in a somewhat limited picture of important aspects of microbial communities. Here, we address this problem by providing a software tool called Mumame, which can distinguish between wildtype and mutated sequences in shotgun metagenomic data and quantify their relative abundances. We demonstrate the utility of the tool by quantifying antibiotic resistance mutations in several publicly available metagenomic data sets. We also identified that sequencing depth is a key factor to detect rare mutations. Therefore, much larger numbers of sequences may be required for reliable detection of mutations than for most other applications of shotgun metagenomics. Mumame is freely available online (http://microbiology.se/software/mumame).

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CircRHOT1 Mediated Cell Proliferation, Apoptosis and Invasion of Pancreatic Cancer Cells by Sponging miR-125a-3p

10.21203/rs.3.rs-19451/v1 ◽

2020 ◽

Author(s):

Sunkai Ling ◽

Yanru He ◽

Xiaoxue Li ◽

Mingyue Hu ◽

Yu Ma ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Biological Function ◽

Diagnostic Marker ◽

Biological Functions ◽

Normal Tissues ◽

Qrt Pcr ◽

Pancreatic Cancer Cells ◽

Cancer Tissues

Abstract Background: The present study aimed to investigate the mechanistic biological function of circRHOT1 in pancreatic cancer cells.Methods: The expression of circRHOT1 and miR-125a-3p in pancreatic cancer tissues and their paired adjacent normal tissues was quantified by qRT-PCR. By knocking down or overexpressing circRHOT1 and miR-125a-3p in pancreatic cancer cells, their functions and potential mechanisms were explored.Results: circRHOT1 was overexpressed in pancreatic cancer tissues and cell lines, and it was found to directly bind to miR-125a-3p, acting as an endogenous sponge to inhibit its activity. Knockdown of circRHOT1 expression significantly inhibited proliferation as well as invasion, and it promoted apoptosis of pancreatic cancer cells via the regulation of E2F3 through the targeting of miR-125a-3p.Conclusion: Taken together, our results demonstrated that circRHOT1 plays critical roles in regulating the biological functions of pancreatic cancer cells, suggesting that circRHOT1 may serve as a potential diagnostic marker and therapeutic target for patients with pancreatic cancer.

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Normas naturales y funciones biológicas

Contrastes Revista Internacional de Filosofía ◽

10.24310/contrastescontrastes.v0i0.1162 ◽

2013 ◽

Author(s):

Cristian Saborido

Keyword(s):

Biological Function ◽

Biological Systems ◽

Philosophy Of Biology ◽

Current Debate ◽

Biological Functions ◽

Naturalistic Account ◽

Organizational Approach

RESUMENEn este trabajo abordo el problema de la fundamentación teórica de la noción de normatividad natural desde una perspectiva naturalista. Presento el debate actual sobre las funciones biológicas en filosofía de la biología, en el cual pueden encontrarse algunos intentos de fundamentar las normas naturales a través del concepto de función biológica. Sostengo que el enfoque predominante etiológico-evolutivo no es capaz justificar la adscripción de normas naturales en los sistemas biológicos y propongo que la nueva perspectiva organizacional está en la mejor posición para ofrecer un tratamiento naturalista de la teleología biológica y de la normatividad natural.PALABRAS CLAVENORMATIVIDAD, FUNCIÓN, NATURALISMO, TELEOLOGÍA, MALFUNCIÓN, ORGANIZACIÓNABSTRACTIn this paper I consider the problem of the theoretical grounding of the notion of natural normativity for the naturalistic perspective. I present the current debate on biological functions in philosophy of biology in which there are some attempts to ground natural norms through the notion of biological function. I argue that the mainstream account, i.e. the evolutive-etiological approach, is not able to ground the ascription of natural norms in biological systems and I defend that the new organizational approach is in the best position to offer an adequate naturalistic account for biological teleology and natural normativity.KEYWORDSNORMATIVITY, FUNCTION, NATURALISM, TELEOLOGYGY, MALFUNCTION, ORGANIZATION

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Biomimetic Drug Delivery Systems Oriented by Biological Function in Tumor Targeting

Current Drug Targets ◽

10.2174/1389450122666210114095859 ◽

2021 ◽

Vol 22 ◽

Author(s):

Rui Wang ◽

Xianyi Sha

Keyword(s):

Drug Delivery ◽

Tumor Targeting ◽

Drug Delivery Systems ◽

Biological Function ◽

Delivery Systems ◽

Biological Functions ◽

Simple Preparation ◽

Targeting Delivery ◽

Clinical Transformation ◽

Endogenous Substances

: The emergence of nanoscale drug delivery systems provides new opportunities for targeting delivery of chemotherapeutic drugs and has achieved excellent results. In recent years, with the arising of the concept of intelligent drug delivery systems, the design and preparation of carriers have become more and more complicated, which is not conducive to clinical transformation. Researchers are gradually focusing on biomimetic nanoscale drug delivery systems, trying to combine the physicochemical properties of nanoscale carriers with the natural biological functions of endogenous substances, so as to boost tumor targeting delivery. In this article, we first classify and introduce biomimetic nanoscale drug delivery systems, and then emphasize their unique biological functions. The biomimetic nanoscale drug delivery systems have the advantages of simple preparation, powerful functions, and low immunogenicity, having a good application prospect.

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Genetic diseases of the Kennedy pathways for membrane synthesis

Journal of Biological Chemistry ◽

10.1074/jbc.rev120.013529 ◽

2020 ◽

Vol 295 (51) ◽

pp. 17877-17886

Author(s):

Mahtab Tavasoli ◽

Sarah Lahire ◽

Taryn Reid ◽

Maren Brodovsky ◽

Christopher R. McMaster

Keyword(s):

Single Gene ◽

Genetic Diseases ◽

Point Mutations ◽

Gene Mutations ◽

Hereditary Diseases ◽

Biological Functions ◽

Phospholipid Synthesis ◽

Spastic Paraplegia ◽

Kennedy Pathway ◽

Single Gene Disorders

The two branches of the Kennedy pathways (CDP-choline and CDP-ethanolamine) are the predominant pathways responsible for the synthesis of the most abundant phospholipids, phosphatidylcholine and phosphatidylethanolamine, respectively, in mammalian membranes. Recently, hereditary diseases associated with single gene mutations in the Kennedy pathways have been identified. Interestingly, genetic diseases within the same pathway vary greatly, ranging from muscular dystrophy to spastic paraplegia to a childhood blinding disorder to bone deformations. Indeed, different point mutations in the same gene (PCYT1; CCTα) result in at least three distinct diseases. In this review, we will summarize and review the genetic diseases associated with mutations in genes of the Kennedy pathway for phospholipid synthesis. These single-gene disorders provide insight, indeed direct genotype-phenotype relationships, into the biological functions of specific enzymes of the Kennedy pathway. We discuss potential mechanisms of how mutations within the same pathway can cause disparate disease.

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Emerging Molecular Biomarkers in Advanced Prostate Cancer: Translation to the Clinic

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_159248 ◽

2016 ◽

pp. 131-141 ◽

Cited By ~ 3

Author(s):

Himisha Beltran ◽

Emmanuel S. Antonarakis ◽

Michael J. Morris ◽

Gerhardt Attard

Keyword(s):

Prostate Cancer ◽

Splice Variants ◽

Wnt Signaling Pathway ◽

Point Mutations ◽

Treatment Resistance ◽

Imaging Biomarkers ◽

Cell Cycle Gene ◽

Castration Resistant Prostate Cancer ◽

Disease Heterogeneity ◽

Improve Risk Stratification

Recent clinical and preclinical studies focused on understanding the molecular landscape of castration-resistant prostate cancer (CRPC) have provided insights into mechanisms of treatment resistance, disease heterogeneity, and potential therapeutic targets. This work has served as a framework for several ongoing clinical studies focused on bringing novel observations into the clinic in the form of tissue, liquid, and imaging biomarkers. Resistance in CRPC typically is driven through reactivation of androgen receptor (AR) signaling, which can occur through AR-activating point mutations, amplification, splice variants (such as AR-V7), or other bypass mechanisms. Detection of AR aberrations in the circulation negatively impacts response to subsequent AR-directed therapies such as abiraterone and enzalutamide. Other potentially clinically relevant alterations in CRPC include defects in DNA damage repair (at either the somatic or germline level) in up to 20% of patients (with implications for PARP1 inhibitor therapy), PI3K/PTEN/Akt pathway activation, WNT signaling pathway alterations, cell cycle gene alterations, and less common but potentially targetable alterations involving RAF and FGFR2. Imaging biomarkers that include those focused on incorporating overexpressed androgen-regulated genes/proteins, such as prostate-specific membrane antigen (PSMA) and dihydrotestosterone (DHT) in combination with CT, can noninvasively identify patterns of AR-driven distribution of CRPC tumor cells, monitor early metastatic lesions, and potentially capture heterogeneity of response to AR-directed therapies and other therapeutics. This article focuses on the current state of clinical biomarker development and future directions for how they might be implemented into the clinic in the near term to improve risk stratification and treatment selection for patients.

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High Sensitive Detection of Imatinib-Resistance Associated Mutations Based on ARMS-PCR.

Blood ◽

10.1182/blood.v104.11.2943.2943 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2943-2943

Author(s):

Franz X.E. Gruber ◽

Mikchail Soevershaev ◽

Marita Olsen ◽

Bjoern Skogen

Keyword(s):

Kinase Inhibitors ◽

Point Mutations ◽

High Sensitivity ◽

Kinase Domain ◽

Single Step ◽

Sensitive Detection ◽

Imatinib Resistance ◽

Abl Kinase ◽

Loop Region ◽

Highly Sensitive Detection

Abstract Background: Point mutations in the Abl kinase domain are associated with resistance against imatinib. Strategies to overcome resistance include dose escalation, combination treatment using imatinib with conventional or other developmental agents or, in the future, imatinib may be replaced by other tyrosine kinase inhibitors which work effectively against mutated clones. Mutational profiling of the BCR-ABL kinase domain will in this scenario become an important analysis as a supplement to BCR-ABL quantitation and may provide the rational basis for therapy, once resistance is diagnosed. Our group reported recently a sensitive, single step PCR assay for quantitation of mutated clones based on the ARMS principle. Aim: We describe an optimized, two step analysis for high sensitivity screening of mutated clones associated with resistance against imatinib targeting all P-Loop mutations, the T315I and M351T. Methods: In a first conventional PCR-reaction a cDNA-region spanning the BCR-ABL breakpoint is amplified resulting in an isolation of the BCR-ABL kinase domain for further analysis. An aliquot is then analysed in a second PCR step, conducted on the real time PCR Taqman platform. Selectivity for the mutated clone is conferred by the amplification refractoriness of non complementary primer 3′-ends (ARMS principle). By introducing potent nucleotide-mismatches in position n-2, selectivity of the assay could be further increased. Even in the P-Loop region, which is known to be a difficult PCR template, misannealing could be reduced to an acceptable level. Results: Assays targeting all P-Loop mutations inclusive the T315I and M351T were tested by analysis of patient samples diluted in normal cDNA and non-mutated BCR-ABL and plasmid dilutions, containing the targeted mutation in a background of wildtype plasmids. Generally a 1:1000 dilution of mutated templates could be detected (sensitivity 0.1%). For some mutations even higher sensitivity could be achieved (0.01%). The level of sensitivity is generally higher than reported for other methods described before. The first PCR step can be conducted in parallel to other PCR-based detection strategies. The second step can be run simultanously to Taqman based BCR-ABL quantitation. This makes the described assay the ideal supplement to general mutation detection approaches like D-HPLC or sequencing strategies. Compared to the single step assay we desribed before, the two step approach increases sensitivity with one or two log factors. Conclusion: The described assay may be suitable for highly sensitive detection of mutated clones in resistant CML patients as a supplement to less sensitive general screening approaches and BCR-ABL quantitation.

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