| 1. |
- Schaller, David, et al.
(författare)
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Corrigendum to “Best match graphs”
- 2021
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Ingår i: Journal of Mathematical Biology. - : Springer Science and Business Media LLC. - 0303-6812 .- 1432-1416. ; 82:6
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Two errors in the article Best Match Graphs (Geiß et al. in JMB 78: 2015–2057, 2019) are corrected. One concerns the tacit assumption that digraphs are sink-free, which has to be added as an additional precondition in Lemma 9, Lemma 11, Theorem 4. Correspondingly, Algorithm 2 requires that its input is sink-free. The second correction concerns an additional necessary condition in Theorem 9 required to characterize best match graphs. The amended results simplify the construction of least resolved trees for n-cBMGs, i.e., Algorithm 1. All other results remain unchanged and are correct as stated.
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| 2. |
- Ariyawansa, Hiran A., et al.
(författare)
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Fungal diversity notes 111–252—taxonomic and phylogenetic contributions to fungal taxa
- 2015
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Ingår i: Fungal diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 75, s. 27-274
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Tidskriftsartikel (refereegranskat)abstract
- This paper is a compilation of notes on 142 fungal taxa, including five new families, 20 new genera, and 100 new species, representing a wide taxonomic and geographic range. The new families, Ascocylindricaceae, Caryosporaceae and Wicklowiaceae (Ascomycota) are introduced based on their distinct lineages and unique morphology. The new Dothideomycete genera Pseudomassariosphaeria (Amniculicolaceae), Heracleicola, Neodidymella and P s e u d o m i c ros p h a e r i o p s i s ( D id y m e l l a c e a e ) , P s e u d o p i t h o m y c e s ( D i d y m o s p h a e r i a c e a e ) , Brunneoclavispora, Neolophiostoma and Sulcosporium (Halotthiaceae), Lophiohelichrysum (Lophiostomataceae), G a l l i i c o l a , Popul o c re s c e n t i a a nd Va g i c o l a (Phaeosphaeriaceae), Ascocylindrica (Ascocylindricaceae), E l o n g a t o p e d i c e l l a t a ( R o u s s o e l l a c e a e ) , Pseudoasteromassaria (Latoruaceae) and Pseudomonodictys (Macrodiplodiopsidaceae) are introduced. The newly described species of Dothideomycetes (Ascomycota) are Pseudomassariosphaeria bromicola (Amniculicolaceae), Flammeascoma lignicola (Anteagloniaceae), Ascocylindrica marina (Ascocylindricaceae) , Lembosia xyliae (Asterinaceae), Diplodia crataegicola and Diplodia galiicola ( B o t r yosphae r i a cea e ) , Caryospor a aquat i c a (Caryosporaceae), Heracleicola premilcurensis and Neodi dymell a thai landi cum (Didymellaceae) , Pseudopithomyces palmicola (Didymosphaeriaceae), Floricola viticola (Floricolaceae), Brunneoclavispora bambusae, Neolophiostoma pigmentatum and Sulcosporium thailandica (Halotthiaceae), Pseudoasteromassaria fagi (Latoruaceae), Keissleriella dactylidicola (Lentitheciaceae), Lophiohelichrysum helichrysi (Lophiostomataceae), Aquasubmersa japonica (Lophiotremataceae) , Pseudomonodictys tectonae (Macrodiplodiopsidaceae), Microthyrium buxicola and Tumidispora shoreae (Microthyriaceae), Alloleptosphaeria clematidis, Allophaeosphaer i a c y t i s i , Allophaeosphae r i a subcylindrospora, Dematiopleospora luzulae, Entodesmium artemisiae, Galiicola pseudophaeosphaeria, Loratospora(Basidiomycota) are introduced together with a new genus Neoantrodiella (Neoantrodiellaceae), here based on both morphology coupled with molecular data. In the class Agaricomycetes, Agaricus pseudolangei, Agaricus haematinus, Agaricus atrodiscus and Agaricus exilissimus (Agaricaceae) , Amanita m e l l e i a l b a , Amanita pseudosychnopyramis and Amanita subparvipantherina (Amanitaceae), Entoloma calabrum, Cora barbulata, Dictyonema gomezianum and Inocybe granulosa (Inocybaceae), Xerocomellus sarnarii (Boletaceae), Cantharellus eucalyptorum, Cantharellus nigrescens, Cantharellus tricolor and Cantharellus variabilicolor (Cantharellaceae), Cortinarius alboamarescens, Cortinarius brunneoalbus, Cortinarius ochroamarus, Cortinarius putorius and Cortinarius seidlii (Cortinariaceae), Hymenochaete micropora and Hymenochaete subporioides (Hymenochaetaceae), Xylodon ramicida (Schizoporaceae), Colospora andalasii (Polyporaceae), Russula guangxiensis and Russula hakkae (Russulaceae), Tremella dirinariae, Tremella graphidis and Tremella pyrenulae (Tremellaceae) are introduced. Four new combinations Neoantrodiella gypsea, Neoantrodiella thujae (Neoantrodiellaceae), Punctulariopsis cremeoalbida, Punctulariopsis efibulata (Punctulariaceae) are also introduced here for the division Basidiomycota. Furthermore Absidia caatinguensis, Absidia koreana and Gongronella koreana (Cunninghamellaceae), Mortierella pisiformis and Mortierella formosana (Mortierellaceae) are newly introduced in the Zygomycota, while Neocallimastix cameroonii and Piromyces irregularis (Neocallimastigaceae) ar e i n t roduced i n the Neocallimastigomycota. Reference specimens or changes in classification and notes are provided for Alternaria ethzedia, Cucurbitaria ephedricola, Austropleospora, Austropleospora archidendri, Byssosphaeria rhodomphala, Lophiostoma caulium, Pseudopithomyces maydicus, Massariosphaeria, Neomassariosphaeria and Pestalotiopsis montellica.
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| 3. |
- Balthazar, Jacqueline T., et al.
(författare)
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A laboratory-based predictive pathway for the development of Neisseria gonorrhoeae high-level resistance to corallopyronin A, an inhibitor of bacterial RNA polymerase
- 2024
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- The continued emergence of Neisseria gonorrhoeae strains that express resistance to multiple antibiotics, including the last drug for empiric monotherapy (ceftriaxone), necessitates the development of new treatment options to cure gonorrheal infections. Toward this goal, we recently reported that corallopyronin A (CorA), which targets the switch region of the β' subunit (RpoC) of bacterial DNA-dependent RNA polymerase (RNAP), has potent anti-gonococcal activity against a panel of multidrug-resistant clinical strains. Moreover, in that study, CorA could eliminate gonococcal infection of primary human epithelial cells and gonococci in a biofilm state. To determine if N. gonorrhoeae could develop high-level resistance to CorA in a single step, we sought to isolate spontaneous mutants expressing any CorA resistance phenotypes. However, no single-step mutants with high-level CorA resistance were isolated. High-level CorA resistance could only be achieved in this study through a multi-step pathway involving over-expression of the MtrCDE drug efflux pump and single amino acid changes in the β and β' subunits (RpoB and RpoC, respectively) of RNAP. Molecular modeling of RpoB and RpoC interacting with CorA was used to deduce how the amino acid changes in RpoB and RpoC could influence gonococcal resistance to CorA. Bioinformatic analyses of whole genome sequences of clinical gonococcal isolates indicated that the CorA resistance determining mutations in RpoB/C, identified herein, are very rare (≤ 0.0029%), suggesting that the proposed pathway for resistance is predictive of how this phenotype could potentially evolve if CorA is used therapeutically to treat gonorrhea in the future. IMPORTANCE: The continued emergence of multi-antibiotic-resistant strains of Neisseria gonorrhoeae necessitates the development of new antibiotics that are effective against this human pathogen. We previously described that the RNA polymerase-targeting antibiotic corallopyronin A (CorA) has potent activity against a large collection of clinical strains that express different antibiotic resistance phenotypes including when such gonococci are in a biofilm state. Herein, we tested whether a CorA-sensitive gonococcal strain could develop spontaneous resistance. Our finding that CorA resistance could only be achieved by a multi-step process involving over-expression of the MtrCDE efflux pump and single amino acid changes in RpoB and RpoC suggests that such resistance may be difficult for gonococci to evolve if this antibiotic is used in the future to treat gonorrheal infections that are refractory to cure by other antibiotics.
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| 4. |
- Bruckmann, Carmen, et al.
(författare)
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From modular decomposition trees to rooted median graphs
- 2022
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Ingår i: Discrete Applied Mathematics. - : Elsevier BV. - 0166-218X .- 1872-6771. ; 310, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- The modular decomposition of a symmetric map δ:X×X→Υ (or, equivalently, a set of pairwise-disjoint symmetric binary relations, a 2-structure, or an edge-colored undirected graph) is a natural construction to capture key features of δ in terms of a labeled tree. A map δ is explained by a vertex-labeled rooted tree (T,t) if the label δ(x,y) coincides with the label of the lowest common ancestor of x and y in T, i.e., if δ(x,y)=t(lca(x,y)). Only maps whose modular decomposition does not contain prime nodes, i.e., the symbolic ultrametrics, can be explained in this manner. Here we consider rooted median graphs as a generalization of (modular decomposition) trees to explain symmetric maps. We derive a linear-time algorithm that stepwisely resolves prime vertices in the modular decomposition tree to obtain a rooted and labeled median graph that explains a given symmetric map δ.
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| 5. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 6. |
- Edwards, Jennifer L., et al.
(författare)
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Potent In Vitro and Ex Vivo Anti-Gonococcal Activity of the RpoB Inhibitor Corallopyronin A
- 2022
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Ingår i: mSphere. - : American Society for Microbiology. - 2379-5042. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Gonorrhea remains a major global public health problem because of the high incidence of infection (estimated 82 million cases in 2020) and the emergence and spread of Neisseria gonorrhoeae strains resistant to previous and current antibiotics used to treat infections. Given the dearth of new antibiotics that are likely to enter clinical practice in the near future, there is concern that cases of untreatable gonorrhea might emerge. In response to this crisis, the World Health Organization (WHO), in partnership with the Global Antibiotic Research and Development Partnership (GARDP), has made the search for and development of new antibiotics against N. gonorrhoeae a priority. Ideally, these antibiotics should also be active against other sexually transmitted organisms, such as Chlamydia trachomatis and/or Mycoplasma genitalium, which are often found with N. gonorrhoeae as co-infections. Corallopyronin A is a potent antimicrobial that exhibits activity against Chlamydia spp. and inhibits transcription by binding to the RpoB switch region. Accordingly, we tested the effectiveness of corallopyronin A against N. gonorrhoeae. We also examined the mutation frequency and modes of potential resistance against corallopyronin A. We report that corallopyronin A has potent antimicrobial action against antibiotic-susceptible and antibiotic-resistant N. gonorrhoeae strains and could eradicate gonococcal infection of cultured, primary human cervical epithelial cells. Critically, we found that spontaneous corallopyronin A-resistant mutants of N. gonorrhoeae are exceedingly rare (≤10-10) when selected at 4× the MIC. Our results support pre-clinical studies aimed at developing corallopyronin A for gonorrheal treatment regimens.IMPORTANCE The high global incidence of gonorrhea, the lack of a protective vaccine, and the emergence of N. gonorrhoeae strains expressing resistance to currently used antibiotics demand that new treatment options be developed. Accordingly, we investigated whether corallopyronin A, an antibiotic which is effective against other pathogens, including C. trachomatis, which together with gonococci frequently cause co-infections in humans, could exert anti-gonococcal action in vitro and ex vivo, and potential resistance emergence. We propose that corallopyronin A be considered a potential future treatment option for gonorrhea because of its potent activity, low resistance development, and recent advances in scalable production.
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| 7. |
- Fernandez-Rozadilla, Ceres, et al.
(författare)
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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
- 2023
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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| 8. |
- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 9. |
- Hellmuth, Marc, 1980-, et al.
(författare)
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Clustering systems of phylogenetic networks
- 2023
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Ingår i: Theory in biosciences. - 1431-7613 .- 1611-7530. ; :142, s. 301-358
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Tidskriftsartikel (refereegranskat)abstract
- Rooted acyclic graphs appear naturally when the phylogenetic relationship of a set X of taxa involves not only speciations but also recombination, horizontal transfer, or hybridization that cannot be captured by trees. A variety of classes of such networks have been discussed in the literature, including phylogenetic, level-1, tree-child, tree-based, galled tree, regular, or normal networks as models of different types of evolutionary processes. Clusters arise in models of phylogeny as the sets C(v) of descendant taxa of a vertex v. The clustering system CN comprising the clusters of a network N conveys key information on N itself. In the special case of rooted phylogenetic trees, T is uniquely determined by its clustering system CT. Although this is no longer true for networks in general, it is of interest to relate properties of N and CN. Here, we systematically investigate the relationships of several well-studied classes of networks and their clustering systems. The main results are correspondences of classes of networks and clustering systems of the following form: If N is a network of type X, then CN satisfies Y, and conversely if C is a clustering system satisfying Y, then there is network N of type X such that C⊆CN.This, in turn, allows us to investigate the mutual dependencies between the distinct types of networks in much detail.
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| 10. |
- Hellmuth, Marc, et al.
(författare)
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Combining Orthology and Xenology Data in a Common Phylogenetic Tree
- 2021
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Ingår i: Advances in Bioinformatics and Computational Biology. - Cham : Springer. - 9783030918132 - 9783030918149 ; , s. 53-64
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Konferensbidrag (refereegranskat)abstract
- In mathematical phylogenetics, types of events in a gene tree T are formalized by vertex labels t(v) and set-valued edge labels λ(e). The orthology and paralogy relations between genes are a special case of a map δ on the pairs of leaves of T defined by δ(x,y)=q if the last common ancestor lca(x,y) of x and y is labeled by an event type q, e.g., speciation or duplication. Similarly, a map εε with m∈ε(x,y) if m∈λ(e) for at least one edge e along the path from lca(x,y) to y generalizes xenology, i.e., horizontal gene transfer. We show that a pair of maps (δ,ε) derives from a tree (T,t,λ) in this manner if and only if there exists a common refinement of the (unique) least-resolved vertex labeled tree (Tδ,tδ) that explains δ and the (unique) least-resolved edge labeled tree (Tε,λε) that explains ε (provided both trees exist). This result remains true if certain combinations of labels at incident vertices and edges are forbidden.
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| 11. |
- Hellmuth, Marc, et al.
(författare)
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Compatibility of partitions with trees, hierarchies, and split systems
- 2022
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Ingår i: Discrete Applied Mathematics. - : Elsevier BV. - 0166-218X .- 1872-6771. ; 314, s. 265-283
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Tidskriftsartikel (refereegranskat)abstract
- The question whether a partition P and a hierarchy H or a tree-like split system S are compatible naturally arises in a wide range of classification problems. In the setting of phylogenetic trees, one asks whether the sets of P coincide with leaf sets of connected components obtained by deleting some edges from the tree T that represents H or S, respectively. More generally, we ask whether a refinement T∗ of T exists such that T∗ and P are compatible in this sense. The latter is closely related to the question as to whether there exists a tree at all that is compatible with P. We report several characterizations for (refinements of) hierarchies and split systems that are compatible with (systems of) partitions. In addition, we provide a linear-time algorithm to check whether refinements of trees and a given partition are compatible. The latter problem becomes NP-complete but fixed-parameter tractable if a system of partitions is considered instead of a single partition. In this context, we also explore the close relationship of the concept of compatibility and so-called Fitch maps.
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| 12. |
- Hellmuth, Marc, et al.
(författare)
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Fitch Graph Completion
- 2023
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Ingår i: Lecture Notes in Computer Science. - 0302-9743 .- 1611-3349. ; , s. 225-237
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Hellmuth, Marc, et al.
(författare)
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Generalized Fitch Graphs III : Symmetrized Fitch maps and Sets of Symmetric Binary Relations that are explained by Unrooted Edge-labeled Trees
- 2021
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Ingår i: Discrete Mathematics & Theoretical Computer Science. - : Centre pour la Communication Scientifique Directe (CCSD). - 1462-7264 .- 1365-8050. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Binary relations derived from labeled rooted trees play an import role in mathematical biology as formal models of evolutionary relationships. The (symmetrized) Fitch relation formalizes xenology as the pairs of genes separated by at least one horizontal transfer event. As a natural generalization, we consider symmetrized Fitch maps, that is, symmetric maps epsilon that assign a subset of colors to each pair of vertices in X and that can be explained by a tree T with edges that are labeled with subsets of colors in the sense that the color m appears in epsilon(x, y) if and only if m appears in a label along the unique path between x and y in T. We first give an alternative characterization of the monochromatic case and then give a characterization of symmetrized Fitch maps in terms of compatibility of a certain set of quartets. We show that recognition of symmetrized Fitch maps is NP-complete. In the restricted case where vertical bar epsilon(x, y)vertical bar <= 1 the problem becomes polynomial, since such maps coincide with class of monochromatic Fitch maps whose graph-representations form precisely the class of complete multi-partite graphs.
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| 14. |
- Hellmuth, Marc, 1980-, et al.
(författare)
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Injective Split Systems
- 2023
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Ingår i: Graphs and Combinatorics. - 0911-0119 .- 1435-5914. ; 39:4
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Tidskriftsartikel (refereegranskat)abstract
- A split system S on a finite set X, |X|≥3, is a set of bipartitions or splits of X which contains all splits of the form {x,X−{x}}, x∈X. To any such split system S we can associate the Buneman graph B(S) which is essentially a median graph with leaf-set X that displays the splits in S. In this paper, we consider properties of injective split systems, that is, split systems S with the property that medB(S)(Y)≠medB(S)(Y′) for any 3-subsets Y,Y′ in X, where medB(S)(Y)med denotes the median in B(S) of the three elements in Y considered as leaves in B(S). In particular, we show that for any set X there always exists an injective split system on X, and we also give a characterization for when a split system is injective. We also consider how complex the Buneman graph B(S) needs to become in order for a split system S on X to be injective. We do this by introducing a quantity for |X| which we call the injective dimension for |X|, as well as two related quantities, called the injective 2-split and the rooted-injective dimension. We derive some upper and lower bounds for all three of these dimensions and also prove that some of these bounds are tight. An underlying motivation for studying injective split systems is that they can be used to obtain a natural generalization of symbolic tree maps. An important consequence of our results is that any three-way symbolic map on X can be represented using Buneman graphs.
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| 15. |
- Huyghe, Jeroen R., et al.
(författare)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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| 16. |
- Kagho, Mervic D., et al.
(författare)
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Total Synthesis via Biomimetic Late-Stage Heterocyclization: Assignment of the Relative Configuration and Biological Evaluation of the Nitraria Alkaloid (±)-Nitrabirine
- 2021
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 86, s. 14903-14914
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Tidskriftsartikel (refereegranskat)abstract
- The racemic total synthesis of nitrabirine (5) together with its previously undescribed epimer 2-epi nitrabirine (5′) is accomplished via a six-step route based on a biomimetic late-stage heterocyclization. This allowed the assignment of the relative configuration of nitrabirine by the lanthanide-induced shifts (LIS) experiment, which was later on confirmed by X-ray diffraction of obtained single crystals. Furthermore, oxidation studies demonstrated that the direct N-oxidation of nitrabirine does not yield nitrabirine N-oxide as reported earlier. In contrast, the reaction of hydrogen peroxide with nitrabirine (5) yields the salt 24′, whereas 2-epi nitrabirine (5′) surprisingly leads to a previously uncharacterized product 22 under the same conditions. Finally, a Fischer indole reaction gave access to novel tetracyclic nitrabirine derivatives 26a-d. A comprehensive biological evaluation of nitrabirine (5), 2-epi nitrabirine (5′), and all derivatives synthesized in this study revealed general biofilm dispersal effects against Candida albicans. Moreover, specific compounds showed moderate antibacterial activities as well as potent cytotoxic activities.
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| 17. |
- Korchmaros, Annachiara, et al.
(författare)
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Quasi-best match graphs
- 2023
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Ingår i: Discrete Applied Mathematics. - : Elsevier BV. - 0166-218X .- 1872-6771. ; 331, s. 104-125
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Tidskriftsartikel (refereegranskat)abstract
- Quasi-best match graphs (qBMGs) are a hereditary class of directed, properly vertex -colored graphs. They arise naturally in mathematical phylogenetics as a generalization of best match graphs, which formalize the notion of evolutionary closest relatedness of genes (vertices) in multiple species (vertex colors). They are explained by rooted trees whose leaves correspond to vertices. In contrast to BMGs, qBMGs represent only best matches at a restricted phylogenetic distance. We provide characterizations of qBMGs that give rise to polynomial-time recognition algorithms and identify the BMGs as the qBMGs that are color-sink-free. Furthermore, two-colored qBMGs are characterized as directed graphs satisfying three simple local conditions, two of which have appeared previously, namely bi-transitivity in the sense of Das et al. (2021) and a hierarchy-like structure of out-neighborhoods, i.e., N(x) n N(y) E {N(x), N(y), 0} for any two vertices x and y. Further results characterize qBMGs that can be explained by binary phylogenetic trees.
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| 18. |
- Loizides, Michael, et al.
(författare)
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Has taxonomic vandalism gone too far? A case study, the rise of the pay-to-publish model and the pitfalls of Morchella systematics
- 2022
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Ingår i: Mycological progress. - : Springer Science and Business Media LLC. - 1617-416X .- 1861-8952. ; 21:1, s. 7-38
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Tidskriftsartikel (refereegranskat)abstract
- The genus Morchella has gone through turbulent taxonomic treatments. Although significant progress in Morchella systematics has been achieved in the past decade, several problems remain unresolved and taxonomy in the genus is still in flux. In late 2019, a paper published in the open-access journal Scientific Reports raised serious concerns about the taxonomic stability of the genus, but also about the future of academic publishing. The paper, entitled “High diversity of Morchella and a novel lineage of the esculenta clade from the north Qinling Mountains revealed by GCPSR-based study” by Phanpadith and colleagues, suffered from gross methodological errors, included false results and artifactual phylogenies, had misapplied citations throughout, and proposed a new species name invalidly. Although the paper was eventually retracted by Scientific Reports in 2021, the fact that such an overtly flawed and scientifically unsound paper was published in a high-ranked Q1 journal raises alarming questions about quality controls and safekeeping procedures in scholarly publishing. Using this paper as a case study, we provide a critical review on the pitfalls of Morchella systematics followed by a series of recommendations for the delimitation of species, description of taxa, and ultimately for a sustainable taxonomy in Morchella. Problems and loopholes in the academic publishing system are also identified and discussed, and additional quality controls in the pre- and post-publication stages are proposed.
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| 19. |
- Miethke, Marcus, et al.
(författare)
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Towards the sustainable discovery and development of new antibiotics
- 2021
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Ingår i: Nature Reviews Chemistry. - : Springer Nature. - 2397-3358. ; 5:10, s. 726-749
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Forskningsöversikt (refereegranskat)abstract
- An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.
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| 20. |
- Murphy, Neil, et al.
(författare)
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Body mass index and molecular subtypes of colorectal cancer
- 2023
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 115:2, s. 165-173
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease.Methods: We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables.Results: Higher BMI was associated with increased CRC risk (OR per 5 kg/m(2) = 1.18, 95% CI = 1.15 to 1.22). The positive association was stronger for men than women but similar across tumor subtypes defined by individual molecular markers. In analyses by Jass type, higher BMI was associated with elevated CRC risk for types 1-4 cases but not for type 5 CRC cases (considered familial-like/Lynch syndrome microsatellite instability-H, CpG island methylator phenotype-low or negative, BRAF-wild type, KRAS-wild type, OR = 1.04, 95% CI = 0.90 to 1.20). This pattern of associations for BMI and Jass types was consistent by sex and design of contributing studies (cohort or case-control).Conclusions: In contrast to previous reports with fewer study participants, we found limited evidence of heterogeneity for the association between BMI and CRC risk according to molecular subtype, suggesting that obesity influences nearly all major pathways involved in colorectal carcinogenesis. The null association observed for the Jass type 5 suggests that BMI is not a risk factor for the development of CRC for individuals with Lynch syndrome.
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| 21. |
- Nounu, Aayah, et al.
(författare)
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A combined proteomics and mendelian randomization approach to investigate the effects of aspirin-targeted proteins on colorectal cancer
- 2021
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : Elsevier. - 1055-9965 .- 1538-7755. ; 30:3, s. 564-575
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence for aspirin’s chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk.Methods: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N ¼ 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N ¼ 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls).Results: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03–1.13; OR: 3.33, 95% CI, 2.46–4.50; and OR: 1.15, 95% CI, 1.02–1.29, respectively).Conclusions: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin’s reduction of metastasis.Impact: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.
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| 22. |
- Nounu, Aayah, et al.
(författare)
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Salicylic Acid and Risk of Colorectal Cancer : A Two-Sample Mendelian Randomization Study
- 2021
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin-use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes' coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR: 1.03, 95% CI: 0.84-1.27 and OR: 1.08, 95% CI: 0.86-1.34, respectively). Results remained unchanged upon aspirin use stratification. We found little evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use.
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| 23. |
- Schaller, David, et al.
(författare)
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A simpler linear-time algorithm for the common refinement of rooted phylogenetic trees on a common leaf set
- 2021
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Ingår i: Algorithms for Molecular Biology. - : Springer Science and Business Media LLC. - 1748-7188. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: The supertree problem, i.e., the task of finding a common refinement of a set of rooted trees is an important topic in mathematical phylogenetics. The special case of a common leaf set L is known to be solvable in linear time. Existing approaches refine one input tree using information of the others and then test whether the results are isomorphic.Results: An O(k|L|) algorithm, LinCR, for constructing the common refinement T of k input trees with a common leaf set L is proposed that explicitly computes the parent function of T in a bottom-up approach.Conclusion: LinCR is simpler to implement than other asymptotically optimal algorithms for the problem and outperforms the alternatives in empirical comparisons.
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| 24. |
- Schaller, David, et al.
(författare)
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Arc-Completion of 2-Colored Best Match Graphs to Binary-Explainable Best Match Graphs
- 2021
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Ingår i: Algorithms. - : MDPI AG. - 1999-4893. ; 14:4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Best match graphs (BMGs) are vertex-colored digraphs that naturally arise in mathematical phylogenetics to formalize the notion of evolutionary closest genes w.r.t. an a priori unknown phylogenetic tree. BMGs are explained by unique least resolved trees. We prove that the property of a rooted, leaf-colored tree to be least resolved for some BMG is preserved by the contraction of inner edges. For the special case of two-colored BMGs, this leads to a characterization of the least resolved trees (LRTs) of binary-explainable trees and a simple, polynomial-time algorithm for the minimum cardinality completion of the arc set of a BMG to reach a BMG that can be explained by a binary tree.
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| 25. |
- Schaller, David, et al.
(författare)
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Best Match Graphs with Binary Trees
- 2021
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Ingår i: Algorithms for Computational Biology. - Cham : Springer. - 9783030744311 - 9783030744328 ; , s. 82-93
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Konferensbidrag (refereegranskat)abstract
- Best match graphs (BMG) are a key intermediate in graph-based orthology detection and contain a large amount of information on the gene tree. We provide a near-cubic algorithm to determine whether a BMG can be explained by a fully resolved gene tree and, if so, to construct such a tree. Moreover, we show that all such binary trees are refinements of the unique binary-resolvable tree (BRT), which in general is a substantial refinement of the also unique least resolved tree of a BMG.
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| 26. |
- Schaller, David, et al.
(författare)
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Best Match Graphs With Binary Trees
- 2023
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Ingår i: IEEE/ACM Transactions on Computational Biology & Bioinformatics. - 1545-5963 .- 1557-9964. ; 20:3, s. 1679-1690
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Tidskriftsartikel (refereegranskat)abstract
- Best match graphs (BMG) are a key intermediate in graph-based orthology detection and contain a large amount of information on the gene tree. We provide a near-cubic algorithm to determine whether a BMG is binary-explainable, i.e., whether it can be explained by a fully resolved gene tree and, if so, to construct such a tree. Moreover, we show that all such binary trees are refinements of the unique binary-refinable tree (BRT), which in general is a substantial refinement of the also unique least resolved tree of a BMG. Finally, we show that the problem of editing an arbitrary vertex-colored graph to a binary-explainable BMG is NP-complete and provide an integer linear program formulation for this task.
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| 27. |
- Schaller, David, et al.
(författare)
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Complete Characterization of Incorrect Orthology Assignments in Best Match Graphs
- 2021
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Ingår i: Journal of Mathematical Biology. - : Springer Science and Business Media LLC. - 0303-6812 .- 1432-1416. ; 82:20
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Tidskriftsartikel (refereegranskat)abstract
- Genome-scale orthology assignments are usually based on reciprocal best matches. In the absence of horizontal gene transfer (HGT), every pair of orthologs forms a reciprocal best match. Incorrect orthology assignments therefore are always false positives in the reciprocal best match graph. We consider duplication/loss scenarios and characterize unambiguous false-positive (u-fp) orthology assignments, that is, edges in the best match graphs (BMGs) that cannot correspond to orthologs for any gene tree that explains the BMG. Moreover, we provide a polynomial-time algorithm to identify all u-fp orthology assignments in a BMG. Simulations show that at least 75% of all incorrect orthology assignments can be detected in this manner. All results rely only on the structure of the BMGs and not on any a priori knowledge about underlying gene or species trees.
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| 28. |
- Schaller, David, et al.
(författare)
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Complexity of modification problems for best match graphs
- 2021
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Ingår i: Theoretical Computer Science. - : Elsevier BV. - 0304-3975 .- 1879-2294. ; 865, s. 63-84
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Tidskriftsartikel (refereegranskat)abstract
- Best match graphs (BMGs) are vertex-colored directed graphs that were introduced to model the relationships of genes (vertices) from different species (colors) given an underlying evolutionary tree that is assumed to be unknown. In real-life applications, BMGs are estimated from sequence similarity data. Measurement noise and approximation errors usually result in empirically determined graphs that in general violate characteristic properties of BMGs. The arc modification problems for BMGs aim at correcting such violations and thus provide a means to improve the initial estimates of best match data. We show here that the arc deletion, arc completion and arc editing problems for BMGs are NP-complete and that they can be formulated and solved as integer linear programs. To this end, we provide a novel characterization of BMGs in terms of triples (binary trees on three leaves) and a characterization of BMGs with two colors in terms of forbidden subgraphs.
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| 29. |
- Schaller, David, et al.
(författare)
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Heuristic algorithms for best match graph editing
- 2021
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Ingår i: Algorithms for Molecular Biology. - : Springer Science and Business Media LLC. - 1748-7188. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Best match graphs (BMGs) are a class of colored digraphs that naturally appear in mathematical phylogenetics as a representation of the pairwise most closely related genes among multiple species. An arc connects a gene x with a gene y from another species (vertex color) Y whenever it is one of the phylogenetically closest relatives of x. BMGs can be approximated with the help of similarity measures between gene sequences, albeit not without errors. Empirical estimates thus will usually violate the theoretical properties of BMGs. The corresponding graph editing problem can be used to guide error correction for best match data. Since the arc set modification problems for BMGs are NP-complete, efficient heuristics are needed if BMGs are to be used for the practical analysis of biological sequence data.Results: Since BMGs have a characterization in terms of consistency of a certain set of rooted triples (binary trees on three vertices) defined on the set of genes, we consider heuristics that operate on triple sets. As an alternative, we show that there is a close connection to a set partitioning problem that leads to a class of top-down recursive algorithms that are similar to Aho’s supertree algorithm and give rise to BMG editing algorithms that are consistent in the sense that they leave BMGs invariant. Extensive benchmarking shows that community detection algorithms for the partitioning steps perform best for BMG editing.Conclusion: Noisy BMG data can be corrected with sufficient accuracy and efficiency to make BMGs an attractive alternative to classical phylogenetic methods.
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| 30. |
- Schaller, David, et al.
(författare)
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Indirect identification of horizontal gene transfer
- 2021
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Ingår i: Journal of Mathematical Biology. - : Springer Science and Business Media LLC. - 0303-6812 .- 1432-1416. ; 83:1
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Tidskriftsartikel (refereegranskat)abstract
- Several implicit methods to infer horizontal gene transfer (HGT) focus on pairs of genes that have diverged only after the divergence of the two species in which the genes reside. This situation defines the edge set of a graph, the later-divergence-time (LDT) graph, whose vertices correspond to genes colored by their species. We investigate these graphs in the setting of relaxed scenarios, i.e., evolutionary scenarios that encompass all commonly used variants of duplication-transfer-loss scenarios in the literature. We characterize LDT graphs as a subclass of properly vertex-colored cographs, and provide a polynomial-time recognition algorithm as well as an algorithm to construct a relaxed scenario that explains a given LDT. An edge in an LDT graph implies that the two corresponding genes are separated by at least one HGT event. The converse is not true, however. We show that the complete xenology relation is described by an rs-Fitch graph, i.e., a complete multipartite graph satisfying constraints on the vertex coloring. This class of vertex-colored graphs is also recognizable in polynomial time. We finally address the question “how much information about all HGT events is contained in LDT graphs” with the help of simulations of evolutionary scenarios with a wide range of duplication, loss, and HGT events. In particular, we show that a simple greedy graph editing scheme can be used to efficiently detect HGT events that are implicitly contained in LDT graphs.
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| 31. |
- Schaller, David, et al.
(författare)
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Least resolved trees for two-colored best match graphs
- 2021
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Ingår i: Journal of Graph Algorithms and Applications. - : Journal of Graph Algorithms and Applications. - 1526-1719. ; 25:1, s. 397-416
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Tidskriftsartikel (refereegranskat)abstract
- In phylogenetic combinatorics, 2-colored best match graphs (2-BMGs) form a subclass of sink-free bi-transitive digraphs that describe the most closely related genes between a pair of species in an evolutionary scenario. They are explained by a unique least resolved tree (LRT). In this paper, the concept of support vertices is introduced and used to derive an O(|V|+|E|log2|V|)-time algorithm that recognizes a 2-BMG and constructs its LRT. The approach can be extended to allow the recognition of binary-explainable 2-BMGs with the same complexity. An empirical comparison emphasizes the efficiency of the new algorithm.
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| 32. |
- Schaller, David, et al.
(författare)
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Orientation of Fitch Graphs and Reconciliation-Free Inference of Horizontal Gene Transfer in Gene Trees
- 2023
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Ingår i: SIAM Journal on Discrete Mathematics. - 0895-4801 .- 1095-7146. ; 37:3, s. 2172-2207
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Tidskriftsartikel (refereegranskat)abstract
- Horizontal gene transfer (HGT) events partition a gene tree T, and thus its leaf set X, into subsets of genes whose evolutionary history is described by speciation and duplication events alone. Two genes thus are xenologs if and only if they belong to two different sets of this partition P. Indirect phylogenetic methods can be used to infer the partition P of X from sequence similarity or evolutionary distances without any a priori knowledge about the underlying tree T. In this contribution, we assume that a partition P of the gene set X and a usually incompletely resolved estimate T of the original gene tree on X are known. We then ask to what extent T and P can be combined to determine the horizontal transfer edges in T and thus the orientation of the HGT events that separate the sets of P. If T and P are compatible, it can be decided for each pair of genes x and y whether there always exists or never exists a horizontal gene transfer in T along the path connecting y and the most recent common ancestor of x and y, and thus a directed edge (x, y) in the so-called Fitch graph of the gene family. We generalize this result to insufficiently resolved gene trees. We show that the classification of a gene pair (x, y) can be computed in constant time after linear-time preprocessing. Using simulated gene family histories, we observe empirically that the vast majority of horizontal transfer edges in the gene tree T can be recovered unambiguously from the knowledge of the partition P. All algorithms developed here are implemented and freely available within the Python package AsymmeTree hosted at https://github.com/david-schaller/AsymmeTree.
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| 33. |
- Schaller, David, et al.
(författare)
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Relative timing information and orthology in evolutionary scenarios
- 2023
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Ingår i: Algorithms for Molecular Biology. - 1748-7188. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evolutionary scenarios describing the evolution of a family of genes within a collection of species comprise the mapping of the vertices of a gene tree T to vertices and edges of a species tree S. The relative timing of the last common ancestors of two extant genes (leaves of T) and the last common ancestors of the two species (leaves of S) in which they reside is indicative of horizontal gene transfers (HGT) and ancient duplications. Orthologous gene pairs, on the other hand, require that their last common ancestors coincides with a corresponding speciation event. The relative timing information of gene and species divergences is captured by three colored graphs that have the extant genes as vertices and the species in which the genes are found as vertex colors: the equal-divergence-time (EDT) graph, the later-divergence-time (LDT) graph and the prior-divergence-time (PDT) graph, which together form an edge partition of the complete graph.ResultsHere we give a complete characterization in terms of informative and forbidden triples that can be read off the three graphs and provide a polynomial time algorithm for constructing an evolutionary scenario that explains the graphs, provided such a scenario exists. While both LDT and PDT graphs are cographs, this is not true for the EDT graph in general. We show that every EDT graph is perfect. While the information about LDT and PDT graphs is necessary to recognize EDT graphs in polynomial-time for general scenarios, this extra information can be dropped in the HGT-free case. However, recognition of EDT graphs without knowledge of putative LDT and PDT graphs is NP-complete for general scenarios. In contrast, PDT graphs can be recognized in polynomial-time. We finally connect the EDT graph to the alternative definitions of orthology that have been proposed for scenarios with horizontal gene transfer. With one exception, the corresponding graphs are shown to be colored cographs.
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| 34. |
- Schmit, Stephanie L, et al.
(författare)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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| 35. |
- Seemann, Carsten R., et al.
(författare)
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Planar median graphs and cubesquare-graphs
- 2023
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Ingår i: Discrete Applied Mathematics. - : Elsevier BV. - 0166-218X .- 1872-6771. ; 331, s. 38-58
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Tidskriftsartikel (refereegranskat)abstract
- Median graphs are connected graphs in which for all three vertices there is a unique vertex that belongs to shortest paths between each pair of these three vertices. In this paper we provide several novel characterizations of planar median graphs. More specifically, we characterize when a planar graph G is a median graph in terms of forbidden subgraphs and the structure of isometric cycles in G, and also in terms of subgraphs of G that are contained inside and outside of 4-cycles with respect to an arbitrary planar embedding of G. These results lead us to a new characterization of planar median graphs in terms of cubesquare-graphs that is, graphs that can be obtained by starting with cubes and square-graphs, and iteratively replacing 4-cycle boundaries (relative to some embedding) by cubes or square-graphs. As a corollary we also show that a graph is planar median if and only if it can be obtained from cubes and square -graphs by a sequence of square-boundaryamalgamations. These considerations also lead to an O(n log n)-time recognition algorithm to compute a decomposition of a planar median graph with n vertices into cubes and square-graphs.
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| 36. |
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| 37. |
- Thomas, Minta, et al.
(författare)
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Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
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| 38. |
- Valdivia, Dulce I., et al.
(författare)
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Hierarchical and modularly-minimal vertex colorings
- 2022
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Ingår i: The Art of Discrete and Applied Mathematics. - : University of Primorska Press. - 2590-9770. ; 6:2, s. #P2.01-#P2.01
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Tidskriftsartikel (refereegranskat)
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| 39. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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