Diminishing Return for Increased Mappability with Longer Sequencing Reads: Implications of the k-mer Distributions in the Human Genome

The amount of non-unique sequence (non-singletons) in a genome directly affects the difficulty of read alignment to a reference assembly for high throughput-sequencing data. Although a greater length increases the chance for reads being uniquely mapped to the reference genome, a quantitative analysis of the influence of read lengths on mappability has been lacking. To address this question, we evaluate the k-mer distribution of the human reference genome. The k-mer frequency is determined for k ranging from 20 to 1000 basepairs. We use the proportion of non-singleton k-mers to evaluate the mappability of reads for a corresponding read length. We observe that the proportion of non-singletons decreases slowly with increasing k, and can be fitted by piecewise power-law functions with different exponents at different k ranges. A faster decay at smaller values for k indicates more limited gains for read lengths > 200 basepairs. The frequency distributions of k-mers exhibit long tails in a power-law-like trend, and rank frequency plots exhibit a concave Zipf's curve. The location of the most frequent 1000-mers comprises 172 kilobase-ranged regions, including four large stretches on chromosomes 1 and X, containing genes with biomedical implications. Even the read length 1000 would be insufficient to reliably sequence these specific regions.Comment: 5 figure

On the role of NOS1 ex1f-VNTR in ADHD – allelic, subgroup, and meta-analysis

Attention deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder featuring complex genetics with common and rare variants contributing to disease risk. In a high proportion of cases, ADHD does not remit during adolescence but persists into adulthood. Several studies suggest that NOS1, encoding nitric oxide synthase I, producing the gaseous neurotransmitter NO, is a candidate gene for (adult) ADHD. We here extended our analysis by increasing the original sample, adding two further samples from Norway and Spain, and conducted subgroup and co-morbidity analysis. Our previous finding held true in the extended sample, and also meta-analysis demonstrated an association of NOS1 ex1fVNTR short alleles with adult ADHD (aADHD). Association was restricted to females, as was the case in the discovery sample. Subgroup analysis on the single allele level suggested that the repeat allele caused the association. Regarding subgroups, we found that NOS1 was associated with the hyperactive/impulsive ADHD subtype, but not to pure inattention. In terms of comorbidity, major depression, anxiety disorders, cluster C personality disorders and migraine were associated with short repeats, in particular the repeat allele. Also, short allele carriers had significantly lower IQ. Finally, we again demonstrated an influence of the repeat on gene expression in human post-mortem brain samples. These data validate the role of NOS-I in hyperactive/impulsive phenotypes and call for further studies into the neurobiological underpinnings of this association.PostprintPeer reviewe

Experimental Evidence of Direct Exchange Interaction Mediating Intramolecular Singlet Fission in Weakly-Coupled Dimers

The electronic interaction between an optically active singlet state ($S_1S_0$) and a dark state of singlet multiplicity, known as correlated triplet pair ($^1[TT]$), plays a crucial role in the effective transformation from $S_1S_0$ to $^1[TT]$ during intramolecular singlet fission (iSF). This process is understood through mechanisms such as direct exchange coupling and incoherent processes that involve super-exchange coupling through charge-transfer states. However, most insights into these mechanisms are derived from theoretical studies due to the difficulties in obtaining experimental evidence. In this study, we investigate the excited-state interactions between $S_1S_0$ and $^1[TT]$ in spiro-conjugated iSF sensitizers by employing transient two-dimensional electronic spectroscopy. This approach allows us to focus on the early stages of the conversion from $S_1S_0$ to $^1[TT]$. Upon optical excitation, a superposition of $S_1S_0$ and $^1[TT]$ is created, which gradually transitions to favor $^1[TT]$ within the characteristic time frames of iSF. The observed high-order signals indicate circular repopulation dynamic that effectively reinitiates the iSF process from higher energy electronic states. Our findings, supported by semi-quantum-mechanical simulations of the experimental data, suggest the presence of a direct iSF mechanism in the dimers, facilitated by weak non-adiabatic coupling between $S_1S_0$ and $^1[TT]$. This experiment provides new insights into the equilibrium between the two electronic states, a phenomenon previously understood primarily through theoretical models.Comment: 26 pages, 4 Figure

Exceptionally High Two-Photon Absorption in Diazaacene-Bithiophene Derivatives: A Combined Experimental and Theoretical Approach

This study delves into the enhancement of two-photon absorption (2PA) properties in diazaacene-bithiophene derivatives through a synergistic approach combining theoretical analysis and experimental validation. By investigating the structural modifications and their impact on 2PA cross sections, we identify key factors that significantly influence the 2PA efficiency. For all molecular systems studied, our state-of-the-art quantum chemical calculations show a very high involvement of the first excited singlet state (S1) in the 2PA processes into higher excited states, even if this state itself has only a small 2PA cross section for symmetry reasons. Consequently, both the oscillator strength of S1 and the transition dipole moments between S1 and other excited states are of importance, underscoring the role of electronic polarizability in facilitating effective two-photon interactions. The investigated compounds exhibit large 2PA cross sections over a wide near-infrared spectral range reaching giant values of 42000 GM. The introduction of diazine and diazaacene moieties into bithiophene derivatives not only induces charge transfer but also opens up pathways for the creation of materials with tailored nonlinear optical responses, suggesting potential applications in nonlinear optics.Comment: 26 pages; 12 figure

Doubly Bridged Anthracenes: Blue Emitters for OLEDs

The photooxidative stability of a series of doubly bridged anthracenes was evaluated after their preparation via twofold macrocyclization of a bis(resorcinyl)anthracene. Lightfastness correlates with the energy levels of the highest occupied molecular orbital (HOMO), resulting in superior stability of the tetraesters compared to the tetraethers. The lengths and steric demand of the linker only plays a minor role for the ester-based compounds, which can be prepared in reasonable yields and thus tested in proof-of-concept organic light-emitting diodes. Double ester-bridging allows deep blue electro-luminescence, highlighting the importance of the choice of the functional groups used for macrocyclization.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Studienstiftung des Deutschen Volkes http://dx.doi.org/10.13039/501100004350Peer Reviewe

Accelerated matrix-vector multiplications for matrices involving genotype covariates with applications in genomic prediction

In the last decade, a number of methods have been suggested to deal with large amounts of genetic data in genomic predictions. Yet, steadily growing population sizes and the suboptimal use of computational resources are pushing the practical application of these approaches to their limits. As an extension to the C/CUDA library miraculix, we have developed tailored solutions for the computation of genotype matrix multiplications which is a critical bottleneck in the empirical evaluation of many statistical models. We demonstrate the benefits of our solutions at the example of single-step models which make repeated use of this kind of multiplication. Targeting modern Nvidia® GPUs as well as a broad range of CPU architectures, our implementation significantly reduces the time required for the estimation of breeding values in large population sizes. miraculix is released under the Apache 2.0 license and is freely available at https://github.com/alexfreudenberg/miraculix

Electrochemical Exfoliation of Graphene and Formation of its Copolyamide 6/66 Nanocomposites by Wet Phase Inversion and Injection Molding

Electrochemically exfoliated graphene (EEG) is compounded with copolyamide 6/66 (PA6/66) to investigate the influence of the carbonaceous filler material on the thermal, rheological, and mechanical properties of the composite. Toward that end, the environmentally friendly electrochemical exfoliation in aqueous solution is further developed to furnish graphene in large quantities. Separating the exfoliation process from the incorporation into the polymer matrix by wet phase inversion (WPI) allowed in-depth characterization of the EEG by scanning electron microscopy (SEM), atomic force microscopy (AFM), and Raman spectroscopy. The crystallinity of copolyamide 6/66-EEG is significantly changed, as revealed by differential scanning calorimetry (DSC). Likewise, the new composite materials exhibit different flow properties, as well as increased mechanical reinforcement with additive concentration. This is proven by dynamic shear rheology and three-point stress tests compared to the neat polymer. Electrochemically exfoliated graphene (EEG) is compounded with copolyamide 6/66 (PA6/66) to investigate its impact on thermal, rheological, and mechanical properties. The electrochemical exfoliation process is optimized for large-scale graphene production. The composite exhibits significant changes in crystallinity, modified flow behavior, and enhanced mechanical reinforcement, as confirmed by differential scanning calorimetry (DSC), rheological analysis, and three-point bending tests. imag