Genes have great significance for the prevention and treatment of some diseases.A vital consideration is the need to find a way to locate pathogenic genes by analyzing the genetic data obtained from different medical ...Genes have great significance for the prevention and treatment of some diseases.A vital consideration is the need to find a way to locate pathogenic genes by analyzing the genetic data obtained from different medical institutions while protecting the privacy of patients’genetic data.In this paper,we present a secure scheme for locating disease-causing genes based on Multi-Key Homomorphic Encryption(MKHE),which reduces the risk of leaking genetic data.First,we combine MKHE with a frequency-based pathogenic gene location function.The medical institutions use MKHE to encrypt their genetic data.The cloud then homomorphically evaluates specific gene-locating circuits on the encrypted genetic data.Second,whereas most location circuits are designed only for locating monogenic diseases,we propose two location circuits(TH-intersection and Top-q)that can locate the disease-causing genes of polygenic diseases.Third,we construct a directed decryption protocol in which the users involved in the homomorphic evaluation can appoint a target user who can obtain the final decryption result.Our experimental results show that compared to the JWB+17 scheme published in the journal Science,our scheme can be used to diagnose polygenic diseases,and the participants only need to upload their encrypted genetic data once,which reduces the communication traffic by a few hundred-fold.展开更多
Identification of disease-causing genes among a large number of candidates is a fundamental challenge in human disease studies.However,it is still time-consuming and laborious to determine the real disease-causing gen...Identification of disease-causing genes among a large number of candidates is a fundamental challenge in human disease studies.However,it is still time-consuming and laborious to determine the real disease-causing genes by biological experiments.With the advances of the high-throughput techniques,a large number of protein-protein interactions have been produced.Therefore,to address this issue,several methods based on protein interaction network have been proposed.In this paper,we propose a shortest path-based algorithm,named SPranker,to prioritize disease-causing genes in protein interaction networks.Considering the fact that diseases with similar phenotypes are generally caused by functionally related genes,we further propose an improved algorithm SPGOranker by integrating the semantic similarity of gene ontology(GO)annotations.SPGOranker not only considers the topological similarity between protein pairs in a protein interaction network but also takes their functional similarity into account.The proposed algorithms SPranker and SPGOranker were applied to 1598 known orphan disease-causing genes from 172 orphan diseases and compared with three state-of-the-art approaches,ICN,VS and RWR.The experimental results show that SPranker and SPGOranker outperform ICN,VS,and RWR for the prioritization of orphan disease-causing genes.Importantly,for the case study of severe combined immunodeficiency,SPranker and SPGOranker predict several novel causal genes.展开更多
The syndrome of multiple morphological abnormalities of the sperm flagella(MMAF)is a specific kind of asthenoteratozoospermia with a mosaic of flagellar morphological abnormalities(absent,short,bent,coiled,and irregul...The syndrome of multiple morphological abnormalities of the sperm flagella(MMAF)is a specific kind of asthenoteratozoospermia with a mosaic of flagellar morphological abnormalities(absent,short,bent,coiled,and irregular flagella).MMAF was proposed in 2014 and has attracted increasing attention;however,it has not been clearly understood.In this review,we elucidate the definition of MMAF from a systematical view,the difference between MMAF and other conditions with asthenoteratozoospermia or asthenozoospermia(such as primary mitochondrial sheath defects and primary ciliary dyskinesia),the knowledge regarding its etiological mechanism and related genetic findings,and the clinical significance of MMAF for intracytoplasmic sperm injection and genetic coun sell ng.This review provides the basic kno wledge for MMAF and puts forward some suggestions for further investigations.展开更多
基金supported by the National Key R&D Program of China(No.2017YFB0802000)the Innovative Research Team in Engineering University of PAP(No.KYTD201805)+2 种基金the National Natural Science Foundation of China(No.61872384)the Natural Science Basic Research Plan in Shaanxi Province of China(No.2020JQ-492)the Fundamental Research Project of Engineering University of PAP(Nos.WJY201910,WJY201914,and WJY201912)。
文摘Genes have great significance for the prevention and treatment of some diseases.A vital consideration is the need to find a way to locate pathogenic genes by analyzing the genetic data obtained from different medical institutions while protecting the privacy of patients’genetic data.In this paper,we present a secure scheme for locating disease-causing genes based on Multi-Key Homomorphic Encryption(MKHE),which reduces the risk of leaking genetic data.First,we combine MKHE with a frequency-based pathogenic gene location function.The medical institutions use MKHE to encrypt their genetic data.The cloud then homomorphically evaluates specific gene-locating circuits on the encrypted genetic data.Second,whereas most location circuits are designed only for locating monogenic diseases,we propose two location circuits(TH-intersection and Top-q)that can locate the disease-causing genes of polygenic diseases.Third,we construct a directed decryption protocol in which the users involved in the homomorphic evaluation can appoint a target user who can obtain the final decryption result.Our experimental results show that compared to the JWB+17 scheme published in the journal Science,our scheme can be used to diagnose polygenic diseases,and the participants only need to upload their encrypted genetic data once,which reduces the communication traffic by a few hundred-fold.
基金supported in part by the National Natural Science Foundation of China(61370024,61428209,61232001)Program for New Century Excellent Talents in University(NCET-12-0547)
文摘Identification of disease-causing genes among a large number of candidates is a fundamental challenge in human disease studies.However,it is still time-consuming and laborious to determine the real disease-causing genes by biological experiments.With the advances of the high-throughput techniques,a large number of protein-protein interactions have been produced.Therefore,to address this issue,several methods based on protein interaction network have been proposed.In this paper,we propose a shortest path-based algorithm,named SPranker,to prioritize disease-causing genes in protein interaction networks.Considering the fact that diseases with similar phenotypes are generally caused by functionally related genes,we further propose an improved algorithm SPGOranker by integrating the semantic similarity of gene ontology(GO)annotations.SPGOranker not only considers the topological similarity between protein pairs in a protein interaction network but also takes their functional similarity into account.The proposed algorithms SPranker and SPGOranker were applied to 1598 known orphan disease-causing genes from 172 orphan diseases and compared with three state-of-the-art approaches,ICN,VS and RWR.The experimental results show that SPranker and SPGOranker outperform ICN,VS,and RWR for the prioritization of orphan disease-causing genes.Importantly,for the case study of severe combined immunodeficiency,SPranker and SPGOranker predict several novel causal genes.
基金This study was supported by grants from the National Natural Science Foundation of China(81771645 and 81471432 to YQT),and Graduate Research and Innovation Projects of Central South University(Grant 2017zzts071 to CFT).
文摘The syndrome of multiple morphological abnormalities of the sperm flagella(MMAF)is a specific kind of asthenoteratozoospermia with a mosaic of flagellar morphological abnormalities(absent,short,bent,coiled,and irregular flagella).MMAF was proposed in 2014 and has attracted increasing attention;however,it has not been clearly understood.In this review,we elucidate the definition of MMAF from a systematical view,the difference between MMAF and other conditions with asthenoteratozoospermia or asthenozoospermia(such as primary mitochondrial sheath defects and primary ciliary dyskinesia),the knowledge regarding its etiological mechanism and related genetic findings,and the clinical significance of MMAF for intracytoplasmic sperm injection and genetic coun sell ng.This review provides the basic kno wledge for MMAF and puts forward some suggestions for further investigations.
