Mathematical Foundations of the Self Organized Neighbor Embedding ({SONE}) for Dimension Reduction and Visualization

Abstract. In this paper we propose the generalization of the recently introduced Neighbor Embedding Exploratory Observation Machine (NE-XOM) for dimension reduction and visualization. We provide a general mathematical framework called Self Organized Neighbor Embedding (SONE).Ittreatsthecomponents, likedatasimilarity measures andneighborhood functions, independently and easily changeable. And it enables the utilization of different divergences, based on the theory of Fréchet derivatives. In this way we propose a new dimension reduction and visualization algorithm, which can be easily adapted to the user specific request and the actual problem.

Single-Site Photocatalytic H-2 Evolution from Covalent Organic Frameworks with Molecular Cobaloxime Co-Catalysts

We demonstrate photocatalytic hydrogen evolution using COF photosensitizers with molecular proton reduction catalysts for the first time. With azine-linked N2-COF photosensitizer, chloro(pyridine)cobaloxime co-catalyst, and TEOA donor, H-2 evolution rate of 782,mu mol h(-1) g(-1) and TON of 54.4 has been obtained in a water/acetonitrile mixture. PXRD, solid-state spectroscopy, EM analysis, and quantum-chemical calculations suggest an outer sphere electron transfer from the COF to the co-catalyst which subsequently follows a monometallic pathway of H-2 generation from the Co-III-hydride and/or Co-II-hydride species

Ausweitung des Sojaanbaus in Deutschland durch züchterische Anpassung sowie pflanzenbauliche und verarbeitungstechnische Optimierung

Die Arbeiten im Sojaforschungsprojekt waren erfolgreich und konnten wichtige Impulse für die Ausweitung des Sojaanbaus in Deutschland geben. So sind die entwickelten Stämme und Kreuzungsnachkommen eine Basis für den Aufbau einer eigenständigen deutschen Sojazüchtung. Die Sorten Korus und Protibus erwiesen sich als besonders geeignet für die Tofuherstellung. Die im Projekt entwickelte Labortofurei ist ein Züchtungsinstrument zur Identifikation vielversprechender Genotypen, mit dem auch die weitere Entwicklung frühreifer Tofusojasorten unterstützt werden kann. In Gefäßversuchen konnte gezeigt werden, dass die Reaktion auf Kühlestress während der Hülsenansatzphase zwischen den Sorten variiert und es tolerante, kompensierende und sensitive Sorten gibt. Die praktische Selektion auf Kältetoleranz war erfolgreich und für die Selektion auf Unkrauttoleranz konnte ein System etabliert werden. Bis auf das Präparat Radicin können die vorhandenen kommerziellen Bradyrhizobienpräparate für den Praxiseinsatz empfohlen werden. Die Hypothese, dass die Selektion des Symbiosepartners auf Kühletoleranz lohnenswert ist, wurde bestätigt. Bei der Sortenprüfung in ganz Deutschland zeigte sich, dass die Anbauwürdigkeit von Soja gut und nur an wenigen der geprüften Standorte nicht gegeben war. Die 00-Sorte ES-Mentor lieferte insgesamt die höchsten Relativerträge sowie den höchsten Rohproteinertrag, bei den 000-Sorten schnitt Sultana besonders gut ab. Eine Variation der Saatzeit sowie verschiedene Verfrühungstechniken erweisen sich nicht als ertragsrelevant. Beim Erfolg der Unkrautregulierung mit Torsionshacke, Fingerhacke und Flachhäufler gab es keine Unterschiede. Im Dammanbau lassen sich Sojabohnen mit gutem Unkrautregulierungserfolg kultivieren. Bei der Sojaaufbereitung sollte eine unnötig hohe Erhitzung der Bohnen bei der Aufbereitung vermieden werden, da durch die Erhitzung neben der Trypsininhibitoraktivität auch Eiweißverdaulichkeit reduziert werden. Mit ausschließlich indirekter, länger einwirkender, trockener Wärme (z. B. Biogasabwärme), ist es schwierig, gute Aufbereitungsqualitäten zu erzielen. Der Wissenstransfer mit Feldtagen und Website www.sojainfo.de war wichtig und erfolgreich zur Steigerung des Interesses am heimischen Sojaanbau

Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data

A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA) in human cancer. Our study employs Whole Genome DNA Sequence (WGS) data from tumor samples (n = 103) to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%), Chr6q27 (16.50%) and Chr18q12.3 (17.48%). Comprehensive mutation screens of genes, lincRNA encoding sequences, control regions and conserved domains within SCNAs demonstrated that a two-hit genetic model was supported in only a minor proportion of recurrent SCNA losses examined (15/40). We found that recurrent breakpoints and regions of inversion often occur within Knudson model SCNAs, leading to the identification of ZNF292 as a target gene for the deletion at 6q14.3-q15 and NKX3.1 as a two-hit target at 8p21.3-p21.2. The importance of alterations of lincRNA sequences was illustrated by the identification of a novel mutational hotspot at the KCCAT42, FENDRR, CAT1886 and STCAT2 loci at the 16q23.1-q24.3 loss. Our data confirm that the burden of SCNAs is predictive of biochemical recurrence, define nine individual regions that are associated with relapse, and highlight the possible importance of ion channel and G-protein coupled-receptor (GPCR) pathways in cancer development. We concluded that a two-hit genetic model accounts for about one third of SCNA indicating that mechanisms, such haploinsufficiency and epigenetic inactivation, account for the remaining SCNA losses

Refphase: Multi-sample phasing reveals haplotype-specific copy number heterogeneity

Most computational methods that infer somatic copy number alterations (SCNAs) from bulk sequencing of DNA analyse tumour samples individually. However, the sequencing of multiple tumour samples from a patient’s disease is an increasingly common practice. We introduce Refphase, an algorithm that leverages this multi-sampling approach to infer haplotype-specific copy numbers through multi-sample phasing. We demonstrate Refphase’s ability to infer haplotype-specific SCNAs and characterise their intra-tumour heterogeneity, to uncover previously undetected allelic imbalance in low purity samples, and to identify parallel evolution in the context of whole genome doubling in a pan-cancer cohort of 336 samples from 99 tumours

Refphase: Multi-Sample Phasing Reveals Haplotype-Specific Copy Number Heterogeneity

Most computational methods that infer somatic copy number alterations (SCNAs) from bulk sequencing of DNA analyse tumour samples individually. However, the sequencing of multiple tumour samples from a patient\u27s disease is an increasingly common practice. We introduce Refphase, an algorithm that leverages this multi-sampling approach to infer haplotype-specific copy numbers through multi-sample phasing. We demonstrate Refphase\u27s ability to infer haplotype-specific SCNAs and characterise their intra-tumour heterogeneity, to uncover previously undetected allelic imbalance in low purity samples, and to identify parallel evolution in the context of whole genome doubling in a pan-cancer cohort of 336 samples from 99 tumours

Reconstructing extrachromosomal DNA structural heterogeneity from long-read sequencing data using Decoil

Circular extrachromosomal DNA (ecDNA) is a form of oncogene amplification found across cancer types and associated with poor outcome in patients. ecDNA can be structurally complex and contain rearranged DNA sequences derived from multiple chromosome locations. As the structure of ecDNA can impact oncogene regulation and may indicate mechanisms of its formation, disentangling it at high resolution from sequencing data is essential. Even though methods have been developed to identify and reconstruct ecDNA in cancer genome sequencing, it remains challenging to resolve complex ecDNA structures, in particular amplicons with shared genomic footprints. We here introduce Decoil, a computational method which combines a breakpoint-graph approach with regression to reconstruct complex ecDNA and deconvolve co-occurring ecDNA elements with overlapping genomic footprints from long-read nanopore sequencing. Decoil outperforms de novo assembly and alignment-based methods in simulated long-read sequencing data for both simple and complex ecDNAs. Applying Decoil on whole genome sequencing data uncovered different ecDNA topologies and explored ecDNA structure heterogeneity in neuroblastoma tumors and cell lines, indicating that this method may improve ecDNA structural analyzes in cancer

MEDICC2: whole-genome doubling aware copy-number phylogenies for cancer evolution

Aneuploidy, chromosomal instability, somatic copy-number alterations, and whole-genome doubling (WGD) play key roles in cancer evolution and provide information for the complex task of phylogenetic inference. We present MEDICC2, a method for inferring evolutionary trees and WGD using haplotype-specific somatic copy-number alterations from single-cell or bulk data. MEDICC2 eschews simplifications such as the infinite sites assumption, allowing multiple mutations and parallel evolution, and does not treat adjacent loci as independent, allowing overlapping copy-number events. Using simulations and multiple data types from 2780 tumors, we use MEDICC2 to demonstrate accurate inference of phylogenies, clonal and subclonal WGD, and ancestral copy-number states