Genome graphs can represent genetic variation and sequence uncertainty. Aligning sequences to genome graphs is key to many applications, including error correction, genome assembly, and genotyping of ...variants in a pangenome graph. Yet, so far, this step is often prohibitively slow. We present GraphAligner, a tool for aligning long reads to genome graphs. Compared to the state-of-the-art tools, GraphAligner is 13x faster and uses 3x less memory. When employing GraphAligner for error correction, we find it to be more than twice as accurate and over 12x faster than extant tools.Availability: Package manager: https://anaconda.org/bioconda/graphaligner and source code: https://github.com/maickrau/GraphAligner.
A study of the strong N−X⋅⋅⋅−O−N+ (X=I, Br) halogen bonding interactions reports 2×27 donor×acceptor complexes of N‐halosaccharins and pyridine N‐oxides (PyNO). DFT calculations were used to ...investigate the X⋅⋅⋅O halogen bond (XB) interaction energies in 54 complexes. A simplified computationally fast electrostatic model was developed for predicting the X⋅⋅⋅O XBs. The XB interaction energies vary from −47.5 to −120.3 kJ mol−1; the strongest N−I⋅⋅⋅−O−N+ XBs approaching those of 3‐center‐4‐electron N−I−N+ halogen‐bonded systems (ca. 160 kJ mol−1). 1H NMR association constants (KXB) determined in CDCl3 and D6acetone vary from 2.0×100 to >108 m−1 and correlate well with the calculated donor×acceptor complexation enthalpies found between −38.4 and −77.5 kJ mol−1. In X‐ray crystal structures, the N‐iodosaccharin‐PyNO complexes manifest short interaction ratios (RXB) between 0.65–0.67 for the N−I⋅⋅⋅−O−N+ halogen bond.
Strong N−X⋅⋅⋅−O−N+ (X=I, Br) halogen bonds, by using oxygen as halogen bond acceptor, are obtained from N‐halosaccharins and aromatic N‐oxides. The donor–acceptor‐dependent tunable X⋅⋅⋅O distances are investigated by using computational methods, solution NMR spectroscopy, and X‐ray diffraction analysis.
N−X⋅⋅⋅−O−N+ halogen‐bonded systems formed by 27 pyridine N‐oxides (PyNOs) as halogen‐bond (XB) acceptors and two N‐halosuccinimides, two N‐halophthalimides, and two N‐halosaccharins as XB donors are ...studied in silico, in solution, and in the solid state. This large set of data (132 DFT optimized structures, 75 crystal structures, and 168 1H NMR titrations) provides a unique view to structural and bonding properties. In the computational part, a simple electrostatic model (SiElMo) for predicting XB energies using only the properties of halogen donors and oxygen acceptors is developed. The SiElMo energies are in perfect accord with energies calculated from XB complexes optimized with two high‐level DFT approaches. Data from in silico bond energies and single‐crystal X‐ray structures correlate; however, data from solution do not. The polydentate bonding characteristic of the PyNOs’ oxygen atom in solution, as revealed by solid‐state structures, is attributed to the lack of correlation between DFT/solid‐state and solution data. XB strength is only slightly affected by the PyNO oxygen properties (atomic charge (Q), ionization energy (Is,min) and local negative minima (Vs,min), as the σ‐hole (Vs,max) of the donor halogen is the key determinant leading to the sequence N‐halosaccharin>N‐halosuccinimide>N‐halophthalimide on the XB strength.
A large data set of X⋅⋅⋅O halogen bonds in N‐haloimide‐pyridine‐N‐oxide complexes has been compiled from 132 DFT‐optimized structures, 75 crystal structures, and 168 1H NMR titrations. This approach has led to unprecedented correlations being found between the DFT halogen bond interaction energies (E) derived from only three key parameters: the sigma‐hole of the XB donor halogen, the atomic charge, and local ionization energies of the oxygen atom.
Rare mononuclear and helical chain low‐valent germanylidene anions supported by cyclic (alkyl)(amino)carbene and hypermetallyl ligands were synthesised by stepwise reduction from corresponding ...germylene precursors via stable and isolable germanium radicals. The electronic structures of the anions can be described with ylidene and ylidone resonance forms with the Ge−C π‐electrons capable of binding even weak electrophiles. The germanylidene anions reacted with CO2 to give μ‐CO2‐κC:κO complexes, a rare coordination mode for low‐valent germanium and inaccessible for the related neutral germylones. These results implicate low‐valent germanylidene anions as efficient single‐site nucleophiles for activation of small molecules.
Stepwise reduction of germylenes via stable and isolable germanium radicals yields germanylidene anions supported by cyclic (alkyl)(amino)carbene and hypermetallyl ligands. The anions contain a highly electron‐rich germanium centre with significant ylidone character and are efficient single‐site nucleophiles that react even with weak electrophiles.
Abstract
Motivation
Graphs are commonly used to represent sets of sequences. Either edges or nodes can be labeled by sequences, so that each path in the graph spells a concatenated sequence. Examples ...include graphs to represent genome assemblies, such as string graphs and de Bruijn graphs, and graphs to represent a pan-genome and hence the genetic variation present in a population. Being able to align sequencing reads to such graphs is a key step for many analyses and its applications include genome assembly, read error correction and variant calling with respect to a variation graph.
Results
We generalize two linear sequence-to-sequence algorithms to graphs: the Shift-And algorithm for exact matching and Myers’ bitvector algorithm for semi-global alignment. These linear algorithms are both based on processing w sequence characters with a constant number of operations, where w is the word size of the machine (commonly 64), and achieve a speedup of up to w over naive algorithms. For a graph with |V| nodes and |E| edges and a sequence of length m, our bitvector-based graph alignment algorithm reaches a worst case runtime of O(|V|+⌈mw⌉|E| log w) for acyclic graphs and O(|V|+m|E| log w) for arbitrary cyclic graphs. We apply it to five different types of graphs and observe a speedup between 3-fold and 20-fold compared with a previous (asymptotically optimal) alignment algorithm.
Availability and implementation
https://github.com/maickrau/GraphAligner
Supplementary information
Supplementary data are available at Bioinformatics online.
PtCl2{Te(CH2)6}2 (1) was synthesized from the cyclic telluroether Te(CH2)6 and cis-PtCl2(NCPh)2 in dichloromethane at room temperature under the exclusion of light. The crystal structure ...determination showed that in the solid state, 1 crystallizes as yellow plate-like crystals of the cis-isomer 1cis and the orange-red interwoven needles of 1trans. The crystals could be separated under the microscope. NMR experiments showed that upon dissolution of the crystals of 1cis in CDCl3, it isomerizes and forms a dynamic equilibrium with the trans-isomer 1trans that becomes the predominant species. Small amounts of cis-trans-Pt3Cl6{Te(CH2)6}4 (2) and cis-trans-Pt4Cl8{Te(CH2)6}4 (3) were also formed and structurally characterized. Both compounds show rare bridging telluroether ligands and two different platinum coordination environments, one exhibiting a cis-Cl/cis-Te(CH2)6 arrangement and the other a trans-Cl/trans-Te(CH2)6 arrangement. Complex 2 has an open structure with two terminal and two bridging telluroether ligands, whereas complex 3 has a cyclic structure with four Te(CH2)6 bridging ligands. The bonding and formation of the complexes have been discussed through the use of DFT calculations combined with QTAIM analysis. The recrystallization of the mixture of the 1:1 reaction from d6-DMSO afforded PtCl2{S(O)(CD3)2}{Te(CH2)6} (4) that could also be characterized both structurally and spectroscopically.
The Te⋅⋅⋅Te secondary bonding interactions (SBIs) in solid cyclic telluroethers were explored by preparing and structurally characterizing a series of Te(CH2)mn (n=1–4; m=3–7) species. The SBIs in ...1,7‐Te2(CH2)10, 1,8‐Te2(CH2)12, 1,5,9‐Te3(CH2)9, 1,8,15‐Te3(CH2)18, 1,7,13,19‐Te4(CH2)20, 1,8,15,22‐Te4(CH2)24 and 1,9,17,25‐Te4(CH2)28 lead to tubular packing of the molecules, as has been observed previously for related thio‐ and selenoether rings. The nature of the intermolecular interactions was explored by solid‐state PBE0‐D3/pob‐TZVP calculations involving periodic boundary conditions. The molecular packing in 1,7,13,19‐Te4(CH2)20, 1,8,15,22‐Te4(CH2)24 and 1,9,17,25‐Te4(CH2)28 forms infinite shafts. The electron densities at bond critical points indicate a narrow range of Te⋅⋅⋅Te bond orders of 0.12–0.14. The formation of the shafts can be rationalized by frontier orbital overlap and charge transfer.
Tubular stacks: The nature of the Te⋅⋅⋅Te chalcogen‐bonding interactions in solid telluroethers 1,7‐Te2(CH2)10, 1,8‐Te2(CH2)12, 1,5,9‐Te3(CH2)9, 1,8,15‐Te3(CH2)18, 1,7,13,19‐Te4(CH2)20, 1,8,15,22‐Te4(CH2)24, and 1,9,17,25‐Te4(CH2)28 was explored by single‐crystal XRD and solid‐state PBE0‐D3/pob‐TZVP calculations involving periodic boundary conditions. Tubular stacking of the larger macrocycles results in the formation of infinite tubular shafts.
The coordination nature of 2‐mono‐ and 2,6‐disubstituted pyridines with electron‐withdrawing halogen and electron‐donating methyl groups for N−X−N+ (X=I, Br) complexations have been studied using 15N ...NMR, X‐ray crystallography, and Density Functional Theory (DFT) calculations. The 15N NMR chemical shifts reveal iodine(I) and bromine(I) prefer to form complexes with 2‐substituted pyridines and only 2,6‐dimethylpyridine. The crystalline halogen(I) complexes of 2‐substituted pyridines were characterized by using X‐ray diffraction analysis, but 2,6‐dihalopyridines were unable to form stable crystalline halogen(I) complexes due to the lower nucleophilicity of the pyridinic nitrogen. In contrast, the halogen(I) complexes of 2,6‐dimethylpyridine, which has a more basic nitrogen, are characterized by X‐crystallography, which complements the 15N NMR studies. DFT calculations reveal that the bond energies for iodine(I) complexes vary between −291 and −351 kJ mol−1 and for bromine between −370 and −427 kJ mol−1. The bond energies of halogen(I) complexes of 2‐halopyridines with more nucleophilic nitrogen are 66‐76 kJ mol−1 larger than those of analogous 2,6‐dihalopyridines with less nucleophilic nitrogen. The experimental and DFT results show that the electronic influence of ortho‐halogen substituents on pyridinic nitrogen leads to a completely different preference for the coordination bonding of halogen(I) ions, providing new insights into bonding in halogen(I) chemistry.
2‐Mono‐ and 2,6‐disubstituted pyridines reveal remarkable bonding preference in linear bis‐coordinate silver(I) and halogen(I) complexes investigated in 15 N NMR solution spectroscopy, X‐ray crystallography, and Density Functional Theory.
TiCp₂S₅ (phase
), TiCp₂Se₅ (phase
), and five solid solutions of mixed titanocene selenide sulfides TiCp₂Se
S₅
(Cp = C₅H₅
) with the initial Se:S ranging from 1:4 to 4:1 (phases
⁻
) were prepared by ...reduction of elemental sulfur or selenium or their mixtures by lithium triethylhydridoborate in thf followed by the treatment with titanocene dichloride TiCp₂Cl₂. Their
Se and
C NMR spectra were recorded from the CS₂ solution. The definite assignment of the
Se NMR spectra was based on the PBE0/def2-TZVPP calculations of the
Se chemical shifts and is supported by
C NMR spectra of the samples. The following complexes in varying ratios were identified in the CS₂ solutions of the phases
⁻
: TiCp₂Se₅ (
₁), TiCp₂Se₄S (
₁), TiCp₂Se₃S₂ (
₁), TiCp₂SSe₃S (
₆), TiCp₂SSe₂S₂ (
₅), TiCp₂SSeS₃ (
₂), and TiCp₂S₅ (
₁). The disorder scheme in the chalcogen atom positions of the phases
⁻
observed upon crystal structure determinations is consistent with the spectral assignment. The enthalpies of formation calculated for all twenty TiCp₂Se
S
(
= 0⁻5) at DLPNO-CCSD(T)/CBS level including corrections for core-valence correlation and scalar relativistic, as well as spin-orbit coupling contributions indicated that within a given chemical composition, the isomers of most favourable enthalpy of formation were those, which were observed by
Se and
C NMR spectroscopy.
The pathways to the formation of the series of RuCl 2 (CO) 2 (ERR′) 2 (E = S, Se, Te; R, R′ = Me, Ph) complexes from RuCl 2 (CO) 3 2 and ERR′ have been explored experimentally in THF and CH 2 Cl 2 ..., and computationally by PBE0-D3/def2-TZVP calculations. The end-products and some reaction intermediates have been isolated and identified by NMR spectroscopy, and their crystal structures have been determined by X-ray diffraction. The relative stabilities of the RuCl 2 (CO) 2 (ERR′) 2 isomers follow the order cct > ccc > tcc > ttt ≈ ctc (the terms c / t refer to cis / trans arrangement of the ligands in the order of Cl, CO, and ERR′). The yields were rather similar in both solvents, but the reactions were significantly faster in THF than in CH 2 Cl 2 . The highest yields were observed for the telluroether complexes, and the yields decreased with lighter chalcogenoethers. PBE0-D3/def2-TZVP calculations indicated that the reaction path is independent of the nature of the solvent. The substitution of one CO ligand of the intermediate RuCl 2 (CO) 3 (ERR′) by the second ERR′ shows the highest activation barrier and is the rate-determining step in all reactions. The observed faster reaction rate in THF than in CH 2 Cl 2 upon reflux can therefore be explained by the higher boiling point of THF. At room temperature the reactions in both solvents proceed equally slowly. When the reaction is carried out in THF, the formation of RuCl 2 (CO) 3 (THF) is also observed, and the reaction may proceed with the substitution of THF by ERR′. The formation of the THF complex, however, is not necessary for the dissociation of the RuCl 2 (CO) 3 2 . Thermal energy at room temperature is sufficient to cleave one of the bridging Ru–Cl bonds. The intermediate thus formed undergoes a facile reaction with ERR′. This mechanism is viable also in non-coordinating CH 2 Cl 2 .
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