Bayesian detection of periodic mRNA time profiles without use of training examples

BACKGROUND: Detection of periodically expressed genes from microarray data without use of known periodic and non-periodic training examples is an important problem, e.g. for identifying genes regulated by the cell-cycle in poorly characterised organisms. Commonly the investigator is only interested in genes expressed at a particular frequency that characterizes the process under study but this frequency is seldom exactly known. Previously proposed detector designs require access to labelled training examples and do not allow systematic incorporation of diffuse prior knowledge available about the period time. RESULTS: A learning-free Bayesian detector that does not rely on labelled training examples and allows incorporation of prior knowledge about the period time is introduced. It is shown to outperform two recently proposed alternative learning-free detectors on simulated data generated with models that are different from the one used for detector design. Results from applying the detector to mRNA expression time profiles from S. cerevisiae showsthat the genes detected as periodically expressed only contain a small fraction of the cell-cycle genes inferred from mutant phenotype. For example, when the probability of false alarm was equal to 7%, only 12% of the cell-cycle genes were detected. The genes detected as periodically expressed were found to have a statistically significant overrepresentation of known cell-cycle regulated sequence motifs. One known sequence motif and 18 putative motifs, previously not associated with periodic expression, were also over represented. CONCLUSION: In comparison with recently proposed alternative learning-free detectors for periodic gene expression, Bayesian inference allows systematic incorporation of diffuse a priori knowledge about, e.g. the period time. This results in relative performance improvements due to increased robustness against errors in the underlying assumptions. Results from applying the detector to mRNA expression time profiles from S. cerevisiae include several new findings that deserve further experimental studies

A strand specific high resolution normalization method for chip-sequencing data employing multiple experimental control measurements

Background: High-throughput sequencing is becoming the standard tool for investigating protein-DNA interactions or epigenetic modifications. However, the data generated will always contain noise due to e. g. repetitive regions or non-specific antibody interactions. The noise will appear in the form of a background distribution of reads that must be taken into account in the downstream analysis, for example when detecting enriched regions (peak-calling). Several reported peak-callers can take experimental measurements of background tag distribution into account when analysing a data set. Unfortunately, the background is only used to adjust peak calling and not as a preprocessing step that aims at discerning the signal from the background noise. A normalization procedure that extracts the signal of interest would be of universal use when investigating genomic patterns. Results: We formulated such a normalization method based on linear regression and made a proof-of-concept implementation in R and C++. It was tested on simulated as well as on publicly available ChIP-seq data on binding sites for two transcription factors, MAX and FOXA1 and two control samples, Input and IgG. We applied three different peak-callers to (i) raw (un-normalized) data using statistical background models and (ii) raw data with control samples as background and (iii) normalized data without additional control samples as background. The fraction of called regions containing the expected transcription factor binding motif was largest for the normalized data and evaluation with qPCR data for FOXA1 suggested higher sensitivity and specificity using normalized data over raw data with experimental background. Conclusions: The proposed method can handle several control samples allowing for correction of multiple sources of bias simultaneously. Our evaluation on both synthetic and experimental data suggests that the method is successful in removing background noise

CHROMIC TRANSITIONS IN PHENYL-SUBSTITUTED POLYTHIOPHENES

The solvatochromic and thermochromic behaviours of phenyl-substituted polythiophenes were studied. The pristine polymers, upon dissolution in chloroform, exhibited blue-shifted absorption. The solid films of the polymers showed significant blue-shifted as well as red-shifted absorptions when heated. While the addition of methanol to the chloroform solutions of the polymers caused dramatic chromic changes and development of red-shifted spectra for many of the polymers investigated, the symmetrically phenyl-substituted and sterically hindered polymer (polymer 1) does not show significant changes. These chromic behaviours have been examined in terms of substituent effects and attempt has been made to explain these effects by calculating the energy barrier for rotation to a planar structure using the HF SCF method and 3-21G* basis set. KEY WORDS: Chromic transitions, Phenyl-substituted polythiophenes Bull. Chem. Soc. Ethiop. 2005, 19(2), 267-276

Revealing cell cycle control by combining model-based detection of periodic expression with novel cis-regulatory descriptors

<p>Abstract</p> <p>Background</p> <p>We address the issue of explaining the presence or absence of phase-specific transcription in budding yeast cultures under different conditions. To this end we use a model-based detector of gene expression periodicity to divide genes into classes depending on their behavior in experiments using different synchronization methods. While computational inference of gene regulatory circuits typically relies on expression similarity (clustering) in order to find classes of potentially co-regulated genes, this method instead takes advantage of known time profile signatures related to the studied process.</p> <p>Results</p> <p>We explain the regulatory mechanisms of the inferred periodic classes with <it>cis</it>-regulatory descriptors that combine upstream sequence motifs with experimentally determined binding of transcription factors. By systematic statistical analysis we show that periodic classes are best explained by combinations of descriptors rather than single descriptors, and that different combinations correspond to periodic expression in different classes. We also find evidence for additive regulation in that the combinations of <it>cis</it>-regulatory descriptors associated with genes periodically expressed in fewer conditions are frequently subsets of combinations associated with genes periodically expression in more conditions. Finally, we demonstrate that our approach retrieves combinations that are more specific towards known cell-cycle related regulators than the frequently used clustering approach.</p> <p>Conclusion</p> <p>The results illustrate how a model-based approach to expression analysis may be particularly well suited to detect biologically relevant mechanisms. Our new approach makes it possible to provide more refined hypotheses about regulatory mechanisms of the cell cycle and it can easily be adjusted to reveal regulation of other, non-periodic, cellular processes.</p

Enhance performance of organic solar cells based on an isoindigo-based copolymer by balancing absorption and miscibility of electron acceptor

Superior absorption of PC(71)BM in visible region to that of PC(61)BM makes PC(71)BM a predominant acceptor for most high efficient polymer solar cells (PSCs). However, we will demonstrate that power conversion efficiencies (PCEs) of PSCs based on poly[N,N'-bis(2-hexyldecyl)isoindigo-6, 6'-diyl-alt-thiophene-2,5-diyl] (PTI-1) with PC(61)BM as acceptor are 50% higher than their PC71BM counterparts under illumination of AM1.5G. AFM images reveal different topographies of the blends between PTI-1:PC(61)BM and PTI-1:PC(71)BM, which suggests that acceptor's miscibility plays a more important role than absorption. The photocurrent of 9.1 mA/cm(2) is among the highest value in PSCs with a driving force for exciton dissociation less than 0.2 eV

Experimental Demonstration of Staggered CAP Modulation for Low Bandwidth Red-Emitting Polymer-LED based Visible Light Communications

In this paper we experimentally demonstrate, for the first time, staggered carrier-less amplitude and phase (sCAP) modulation for visible light communication systems based on polymer light-emitting diodes emitting at ~639 nm. The key advantage offered by sCAP in comparison to conventional multiband CAP is its full use of the available spectrum. In this work, we compare sCAP, which utilises four orthogonal filters to generate the signal, with a conventional 4-band multi-CAP system and on-off keying (OOK). We transmit each modulation format with equal energy and present a record un-coded transmission speed of ~6 Mb/s. This represents gains of 25% and 65% over the achievable rate using 4-CAP and OOK, respectively.Comment: 6 pages, 9 figures, IEEE ICC 2019 conferenc

Novel rhodanine based molecular acceptor for organic solar cells

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.A dirhodanine-substituted benzothiadiazole compound has been synthesised using Knoevenagel condensation of a dialdehyde-substituted benzothiadiazole and rhodanine. The resulting compound was deep orange red in colour and shows a HOMO and LUMO levels of −5.61 and −3.85 eV respectively, which makes it suitable for applications such as acceptor for organic solar cells

Small Band Gap Polymers Synthesized via a Modified Nitration of 4,7-Dibromo-2,1,3-benzothiadiazole

The nitration of 4,7-dibromo-2,1,3-benzothiadiazole was modified by using CF3SO3H and HNO3 as the nitrating agent, and the related yield was improved greatly. On the basis of this improvement, two new small band gap polymers, P1TPQ and P3TPQ, were developed. Bulk heterojunction solar cells based on P3TPO and [6,6]-phenyl-C-71-butyric acid methyl ester exhibit interesting results with a power conversion efficiency of 21% and photoresponse up to 1.1 mu

Pyrrolo 3,4-g quinoxaline-6,8-dione-based conjugated copolymers for bulk heterojunction solar cells with high photovoltages

A new electron-deficient building block 5,9-di(thiophen-2-yl)-6H-pyrrolo[3,4-g]quinoxaline-6,8(7H)-dione (PQD) was synthesized via functionalizing the 6- and 7-positions of quinoxaline (Qx) with a dicarboxylic imide moiety. Side chain substitution on the PQD unit leads to good solubility which enables very high molecular weight copolymers to be attained. The fusion of two strong electron-withdrawing groups (Qx and dicarboxylic imide) makes the PQD unit a stronger electron-deficient moiety than if the unit had just one electron-withdrawing group, thus enhancing the intramolecular charge transfer between electron-rich and deficient units of the copolymer. Four PQD-based polymers were synthesized which feature deep-lying highest occupied molecular orbital (HOMO) levels and bathochromic absorption spectra when compared to PBDT-Qx and PBDT-TPD analogues. The copolymers incorporated with benzo[1,2-b:4,5-b']dithiophene (BDT) units show that the 1D and 2D structural variations of the side groups on the BDT unit are correlated with the device performance. As a result, the corresponding solar cells (ITO/PEDOT:PSS/polymer: PC71BM/LiF/Al) based on the four copolymers feature very high open-circuit voltages (V-oc) of around 1.0 V. The copolymer PBDT-PQD1 attains the best power conversion efficiency of 4.9%, owing to its relatively high absorption intensity and suitable film morphology. The structure-property correlation demonstrates that the new PQD unit is a promising electron-deficient building block for efficient photovoltaic materials with high V-oc

Spatiotemporal variations in retrovirus-host interactions among Darwin's finches

Endogenous retroviruses (ERVs) are inherited remnants of retroviruses that colonized host germline over millions of years, providing a sampling of retroviral diversity across time. Here, we utilize the strength of Darwin's finches, a system synonymous with evolutionary studies, for investigating ERV history, revealing recent retrovirus-host interactions in natural populations. By mapping ERV variation across all species of Darwin's finches and comparing with outgroup species, we highlight geographical and historical patterns of retrovirus-host occurrence, utilizing the system for evaluating the extent and timing of retroviral activity in hosts undergoing adaptive radiation and colonization of new environments. We find shared ERVs among all samples indicating retrovirus-host associations pre-dating host speciation, as well as considerable ERV variation across populations of the entire Darwin's finches' radiation. Unexpected ERV variation in finch species on different islands suggests historical changes in gene flow and selection. Non-random distribution of ERVs along and between chromosomes, and across finch species, suggests association between ERV accumulation and the rapid speciation of Darwin's finches.Endogenous retroviruses (ERV) are inherited remains of retroviruses that have colonized host genomes during evolution. Here the authors observe considerable species-specific ERV variation among Darwin's finches, reflecting historic retrovirus-host interactions