SubMo-GNN: Property- and Structure-Aware Diverse Molecular Selection with Representation Learning and Mathematical Diverse-Selection Framework

Selecting diverse molecules from unexplored areas of chemical space is one of the most important tasks for discovering novel molecules and reactions. This paper develops a new method for selecting a diverse subset of molecules from a given molecular list by utilizing two techniques studied in machine learning and mathematical optimization: graph neural networks (GNNs) for learning vector representation of molecules and a diverse-selection framework called submodular function maximization. Our method first trains a GNN with property prediction tasks, and then the trained GNN transforms molecular graphs into molecular vectors, which capture both properties and structures of molecules. Finally, to obtain a diverse subset of molecules, we define a submodular function, which quantifies the diversity of molecular vectors, and find a subset of molecular vectors with a large submodular function value. This can be done efficiently by using the greedy algorithm, and the diversity of selected molecules measured by the submodular function value is mathematically guaranteed to be at least 63 % of that of an optimal selection. We also introduce a new evaluation criterion to measure the diversity of selected molecules based on molecular properties. Computational experiments confirm that our method successfully selects diverse molecules from the QM9 dataset regarding the property-based criterion, while performing comparably to existing methods regarding a standard structure-based criterion. The proposed method enables researchers to obtain diverse sets of molecules for discovering new molecules and novel chemical reactions, and the proposed diversity criterion is useful for discussing the diversity of molecular libraries from a new property-based perspective.

Single Nucleotide Polymorphims (snps) Identification of Inhibin Sub Unit-α (inha) Gene on Madura Bulls

INHA gene is a gene that is suggested to have role in reproductive system. Single Nucleotide Polymorphisms (SNPs) of Madura Bulls were identified in this study. Polymerase Chain Reactions (PCR) was used to amplify INHA gene region and MEGA 7 program was utilized to align the amplified region sequences with sequence from Ensembl database. Four SNPs found in INHA and they are located at the first exon. Two SNPs were misssense mutations that causing the substitution of amino acid leucine21 by proline, and amino acid valine63 by methionine and the other two SNPs were synonymous mutation. One of the synonymous SNPs was a novel mutation. Based on those identified SNPs, they could be suggested as potential candidate markers of reproduction traits for Madura bulls. Moreover, through heterozygosity value from the observed bulls, it was indicated that the genotype was varied in population. Therefore a molecular selection program could be designed to determine the Madura superior bull.

Polymorphism Exploration of Growth Family (GH, GHRH and PIT-1) Genes Polymorphisms of Local Swamp Buffalo for Productivity Improvement in North Tapanuli Regency, North Sumatra

Genetic improvement of livestock productivity can be done through molecular selection on the genes controlling growth traits. Genetic polymorphism of the growth family (GH, GHRH, and PIT1) genes were studied in local swamp buffalo (106 hds.) from a government buffalo breeding station (46 heads) and smallholders (60 heads) in North Tapanuli District, North Sumatra Province. Genotype variants of the three genes were identified by PCR-RFLP method using restriction enzymes of MspI (GH gene), HaeIII (GHRH gene) and HinfI (PIT -1 gene). Genotyping on individual GH_g.1547T>C, GHRH_g.4666G>C, and PIT -1_g.1256G >A loci resulted only one type genotype, respectively TT, CC, an d AA, with one type of allele, respectively T, C, and A. Heterozygosity observation (Ho) and expectation (He) values values and the PIC value for each locus was 0.00. It could be suggested to increase genotype frequenciest of the three growth genes that are positively associated with the growth traits and economic traits of the buffalo.

Recent advancement of molecular breeding for improving salinity tolerance in wheat.

This chapter provides an outline of the mechanisms of wheat salinity tolerance and discusses the challenges of several breeding programmes that are in progress with regard to durum (Triticum turgidum subsp. durum) and bread wheats using the integration of trait-based and molecular selection for delivering improved wheat varieties adapted to saline conditions.

Polymorphism of CSN1S1 (g.12164G>A) and CSN2 (g.8913C>A) genes in pure and cross dairy goats

Casein genes directly control milk protein of animals. CSN1S1 (αS1-Casein) and CSN2 (β-Casein) genes influence on milk protein fractions. Genetic polymorphisms of CSN1S1 gene at g.12164G>A locus and CSN2 gene at g.8913C>A locus were identified by PCR-RFLP technique. Animal samples were pure dairy goats providing PE (5 hds.), Saanen (8 hds.) and their crosses providing Sapera (50% Saanen, 50% PE) (51 hds.) and SaanPE (75% Saanen, 25% PE) (3 hds.) from IRIAP dairy goat station. Allele frequency, genotype frequency, heterozygosity value, and Hardy-Weinberg (H-W) equilibrium value were analyzed by Popgen32 program. CSN1S1_g.12164G>A locus resulted in two alleles, i.e. G allele (192 bp, 145 bp, and 101 bp) and A allele (337 bp and 101 bp). The G allele from the highest frequenciest was successively Saanen (0.625), Sapera (0.578), PE (0.400), and SaanPE (0.333). Most dairy goats were heterozygote (Ho>He) and in H-W equilibrium (q2 count < q2P0.05). Whereas CSN2_g.8913C>A locus was monomorphic for possesing only C allele (233 bp and 162 bp), without A allele (416 bp). The existent g.12164G>A SNP of the CSN1S1 gene of could be a potencial molecular selection marker of milk protein content in dairy goat.

Influence of energy gap between charge-transfer and locally excited states on organic long persistence luminescence

Organic long-persistent luminescence (LPL) is an organic luminescence system that slowly releases stored exciton energy as light. Organic LPL materials have several advantages over inorganic LPL materials in terms of functionality, flexibility, transparency, and solution-processability. However, the molecular selection strategies for the organic LPL system still remain unclear. Here we report that the energy gap between the lowest localized triplet excited state and the lowest singlet charge-transfer excited state in the exciplex system significantly controls the LPL performance. Changes in the LPL duration and spectra properties are systematically investigated for three donor materials having a different energy gap. When the energy level of the lowest localized triplet excited state is much lower than that of the charge-transfer excited state, the system exhibits a short LPL duration and clear two distinct emission features originating from exciplex fluorescence and donor phosphorescence.

INNV-41. PROSPECTIVE SELECTION OF RECURRENT GLIOBLASTOMA PATIENTS FOR TAILORED THERAPIES. RESULTS OF AN INSTITUTIONAL EXPERIENCE

INTRODUCTION Failure of clinical trials with targeted therapies in glioblastoma (GBM) is probably due to the enrollment of molecularly unselected patients. In preliminary studies, we prospectively selected recurrent GBM patients on the basis of molecular pattern and administered targeted therapy accordingly. This tailored approach gave encouraging results in term of low recurrence rate (RR) and high 6-month progression free survival (PFS-6). Here, we present the long-term results of our work. METHODS On recurrent tumor samples of 34 adult patients, we assessed the expression of VEGF and PTEN through immunohistochemistry and of EGFRvIII through RT-PCR. Patients with VEGF overexpression were treated with bevacizumab (10 mg/Kg i.v. every 2 weeks in 6-week cycles). Patients with EGFRvIII expression and normal PTEN expression added erlotinib (150 mg/day orally). Patients with loss of PTEN expression, irrespective of EGFRvIII status, added sirolimus (1–10 mg/day orally). RESULTS Sixteen patients received bevacizumab alone (bev), 14 bevacizumab plus erlotinib (bev+erl) and 4 bevacizumab plus sirolimus (bev+sir). RR was 50% in the whole cohort and 37.5%, 57.1% and 75% in bev, bev+erl and bev+sir groups, respectively. PFS-6 was 55.9% in the whole cohort and 50%, 64.3% and 50% in bev, bev+erl and bev+sir groups, respectively. Our data compare favorably with those from the large EORTC 26101 trial, which showed a RR of 41.5% and a PFS-6 lower than 30%. When considering sustained response (defined as PFS ≥ 12 months), we overall observed a 20.6% rate, with the highest value in bev+erl subgroup (28.6%). Interestingly, in EORTC 26101 trial, less than 10% of patients achieved PFS ≥ 12 months. CONCLUSIONS Our results confirm that the tailored approach in recurrent GBM provides an advantage in terms of RR, PFS and, above all, of long-term responses, compared with trials without molecular selection.

Genetic Polymorphism of SCD1 Gene of Holstein-Friesian Cows in Indonesia

<p class="abstrak2">Stearoyl-Coenzyme A desaturase 1 (SCD1) belongs to the fatty acid family of desaturases. In lactating ruminants, the SCD1 protein is highly expressed in the mammary gland and is relevant for the fatty acid composition of milk and dairy products. Polymorphism of SCD1 gene in Holstein-Friesian (HF) cows could be used as a basis of molecular selection of cattle in order to increase their productivity. The aim of this study was to investigate the polymorphism of SCD1 gene of Holstein-Friesian cows in Indonesia. A total of 162 blood samples of HF cows were collected from four different locations i.e. Bogor, Sukabumi, Tasikmalaya and Enrekang districts. Genotyping of SCD1 gene used PCR-RFLP method with NcoI restriction enzyme. The result showed that three genotypes (AA, AV and VV) and two alleles (A and V) have successfully found and polymorphic. A allele was dominant in all populations (0.63) and in Hardy Weinberg Equilibrium. The highest A allele was found in Sukabumi (0.78) and the lowest was in Bogor (0.55). Heterozigosity observed and expected reached 0.471 and 0.470, respectively. In conclusion, genetic polymorphism was found in all population with dominant of A allele. This finding can be used as a early genetic information of Holstein-Friesian cattle in Indonesia and to build breeding strategy for improving of productivity especially improving of healthy fat milk. </p><p class="abstrak2"><span><br /></span></p>

Selective Nucleobase Pairing Extends Plausible Prebiotic Conditions to the Solid State

<div>Pairing of complementary nucleobases is the most famous example of molecular recognition. However, it has long been known that except 9-methyladenine (9-mA) and 1-methylthymine (1-mT), all other binary combinations of nucleobases do not form base pairs under plausible prebiotic conditions, e.g., in water or in the solid state. It is surprising that nucleobases would have been incorporated into DNA if they were unable to self-assemble prior to their attachment. Here we show how the formation of an elusive base pair between 9-methylguanine (9-mG) and 1-methylcytosine (1-mC) is possible in the solid state via Watson-Crick hydrogen bonding. Molecular recognition of 9-mG:1-mC as well as 9-mA:1-mT base pairs was observed by X-ray diffraction monitoring during heating their 1:1 solid mixtures, while all other binary mixtures failed to give base pairs. To demonstrate the selectivity of complementary nucleobase pairing, we showed how 9-mA and 1-mT self-assembled in ternary mixture containing also 1-methyluracil (1-mU), and both 9-mA:1-mT and 9-mG:1-mC pairs self-assembled in quaternary mixture. The results presented here indicate the importance that the solid state as a reaction medium might have had as a prebiotic molecular selection tool towards compatibility as found in the DNA.</div>