Neuro-Symbolic Deductive Reasoning for Cross-Knowledge Graph Entailment

A significant and recent development in neural-symbolic learning are deep neural networks that can reason over symbolic knowledge graphs (KGs). A particular task of interest is KG entailment, which is to infer the set of all facts that are a logical consequence of current and potential facts of a KG. Initial neural-symbolic systems that can deduce the entailment of a KG have been presented, but they are limited: current systems learn fact relations and entailment patterns specific to a particular KG and hence do not truly generalize, and must be retrained for each KG they are tasked with entailing. We propose a neural-symbolic system to address this limitation in this paper. It is designed as a differentiable end-to-end deep memory network that learns over abstract, generic symbols to discover entailment patterns common to any reasoning task. A key component of the system is a simple but highly effective normalization process for continuous representation learning of KG entities within memory networks. Our results show how the model, trained over a set of KGs, can effectively entail facts from KGs excluded from the training, even when the vocabulary or the domain of test KGs is completely different from the training KGs

TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association wit

The transcriptional landscape of Shh medulloblastoma

© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.info:eu-repo/semantics/publishedVersio

Neuro-Symbolic Deductive Reasoning for Cross-Knowledge Graph Entailment

A significant and recent development in neural-symbolic learning are deep neural networks that can reason over symbolic knowledge graphs (KGs). A particular task of interest is KG entailment, which is to infer the set of all facts that are a logical consequence of current and potential facts of a KG. Initial neural-symbolic systems that can deduce the entailment of a KG have been presented, but they are limited: current systems learn fact relations and entailment patterns specific to a particular KG and hence do not truly generalize, and must be retrained for each KG they are tasked with entailing. We propose a neural-symbolic system to address this limitation in this paper. It is designed as a differentiable end-to-end deep memory network that learns over abstract, generic symbols to discover entailment patterns common to any reasoning task. A key component of the system is a simple but highly effective normalization process for continuous representation learning of KG entities within memory networks. Our results show how the model, trained over a set of KGs, can effectively entail facts from KGs excluded from the training, even when the vocabulary or the domain of test KGs is completely different from the training KGs