MVP predicts the pathogenicity of missense variants by deep learning.

Abstract:

:Accurate pathogenicity prediction of missense variants is critically important in genetic studies and clinical diagnosis. Previously published prediction methods have facilitated the interpretation of missense variants but have limited performance. Here, we describe MVP (Missense Variant Pathogenicity prediction), a new prediction method that uses deep residual network to leverage large training data sets and many correlated predictors. We train the model separately in genes that are intolerant of loss of function variants and the ones that are tolerant in order to take account of potentially different genetic effect size and mode of action. We compile cancer mutation hotspots and de novo variants from developmental disorders for benchmarking. Overall, MVP achieves better performance in prioritizing pathogenic missense variants than previous methods, especially in genes tolerant of loss of function variants. Finally, using MVP, we estimate that de novo coding variants contribute to 7.8% of isolated congenital heart disease, nearly doubling previous estimates.

journal_name

Nat Commun

journal_title

Nature communications

authors

Qi H,Zhang H,Zhao Y,Chen C,Long JJ,Chung WK,Guan Y,Shen Y

doi

10.1038/s41467-020-20847-0

subject

Has Abstract

pub_date

2021-01-21 00:00:00

pages

510

issue

1

issn

2041-1723

pii

10.1038/s41467-020-20847-0

journal_volume

12

pub_type

杂志文章
  • Efficient green light-emitting diodes based on quasi-two-dimensional composition and phase engineered perovskite with surface passivation.

    abstract::Perovskite light-emitting diodes (LEDs) are attracting great attention due to their efficient and narrow emission. Quasi-two-dimensional perovskites with Ruddlesden-Popper-type layered structures can enlarge exciton binding energy and confine charge carriers and are considered good candidate materials for efficient LE...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-02978-7

    authors: Yang X,Zhang X,Deng J,Chu Z,Jiang Q,Meng J,Wang P,Zhang L,Yin Z,You J

    更新日期:2018-02-08 00:00:00

  • Replication stress triggers microsatellite destabilization and hypermutation leading to clonal expansion in vitro.

    abstract::Mismatch repair (MMR)-deficient cancers are characterized by microsatellite instability (MSI) and hypermutation. However, it remains unclear how MSI and hypermutation arise and contribute to cancer development. Here, we show that MSI and hypermutation are triggered by replication stress in an MMR-deficient background,...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-11760-2

    authors: Matsuno Y,Atsumi Y,Shimizu A,Katayama K,Fujimori H,Hyodo M,Minakawa Y,Nakatsu Y,Kaneko S,Hamamoto R,Shimamura T,Miyano S,Tsuzuki T,Hanaoka F,Yoshioka KI

    更新日期:2019-09-02 00:00:00

  • A spin-liquid with pinch-line singularities on the pyrochlore lattice.

    abstract::The mathematics of gauge theories lies behind many of the most profound advances in physics in the past 200 years, from Maxwell's theory of electromagnetism to Einstein's theory of general relativity. More recently it has become clear that gauge theories also emerge in condensed matter, a prime example being the spin-...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms11572

    authors: Benton O,Jaubert LD,Yan H,Shannon N

    更新日期:2016-05-26 00:00:00

  • Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis.

    abstract::Gut-associated inflammation plays a crucial role in the progression of colon cancer. Here, we identify a novel pathogen-host interaction that promotes gut inflammation and the development of colon cancer. We find that enteropathogenic bacteria-secreted particles (ET-BSPs) stimulate intestinal epithelium to produce IDE...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7956

    authors: Deng Z,Mu J,Tseng M,Wattenberg B,Zhuang X,Egilmez NK,Wang Q,Zhang L,Norris J,Guo H,Yan J,Haribabu B,Miller D,Zhang HG

    更新日期:2015-04-24 00:00:00

  • MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment.

    abstract::Rather than targeting tumour cells directly, elements of the tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here we report a unique mechanism by which ectopic microRNA-103 can manipulate tumour-associated endothelial cells to enhance tumour cell death. Using gain-and-loss of f...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms13597

    authors: Wilson R,Espinosa-Diez C,Kanner N,Chatterjee N,Ruhl R,Hipfinger C,Advani SJ,Li J,Khan OF,Franovic A,Weis SM,Kumar S,Coussens LM,Anderson DG,Chen CC,Cheresh DA,Anand S

    更新日期:2016-11-25 00:00:00

  • Efficient and stable sky-blue delayed fluorescence organic light-emitting diodes with CIEy below 0.4.

    abstract::Organic light-emitting diodes utilizing thermally activated delayed fluorescence is a potential solution for achieving stable blue devices. Sky-blue devices (CIEy < 0.4) with high stability and high external quantum efficiency (>15%) at 1000 cd m-2 based on either delayed fluorescence or phosphorescence are still limi...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07482-6

    authors: Chan CY,Tanaka M,Nakanotani H,Adachi C

    更新日期:2018-11-28 00:00:00

  • Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle.

    abstract::The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on n...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-12080-1

    authors: Brouwer PJM,Antanasijevic A,Berndsen Z,Yasmeen A,Fiala B,Bijl TPL,Bontjer I,Bale JB,Sheffler W,Allen JD,Schorcht A,Burger JA,Camacho M,Ellis D,Cottrell CA,Behrens AJ,Catalano M,Del Moral-Sánchez I,Ketas TJ,LaBranche

    更新日期:2019-09-19 00:00:00

  • Actively evolving subglacial conduits and eskers initiate ice shelf channels at an Antarctic grounding line.

    abstract::Ice-shelf channels are long curvilinear tracts of thin ice found on Antarctic ice shelves. Many of them originate near the grounding line, but their formation mechanisms remain poorly understood. Here we use ice-penetrating radar data from Roi Baudouin Ice Shelf, East Antarctica, to infer that the morphology of severa...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms15228

    authors: Drews R,Pattyn F,Hewitt IJ,Ng FSL,Berger S,Matsuoka K,Helm V,Bergeot N,Favier L,Neckel N

    更新日期:2017-05-09 00:00:00

  • Selective isolation of gold facilitated by second-sphere coordination with α-cyclodextrin.

    abstract::Gold recovery using environmentally benign chemistry is imperative from an environmental perspective. Here we report the spontaneous assembly of a one-dimensional supramolecular complex with an extended {[K(OH₂)₆][AuBr₄](α-cyclodextrin)₂}n chain superstructure formed during the rapid co-precipitation of α-cyclodextrin...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms2891

    authors: Liu Z,Frasconi M,Lei J,Brown ZJ,Zhu Z,Cao D,Iehl J,Liu G,Fahrenbach AC,Botros YY,Farha OK,Hupp JT,Mirkin CA,Fraser Stoddart J

    更新日期:2013-01-01 00:00:00

  • Osteoclast-associated receptor blockade prevents articular cartilage destruction via chondrocyte apoptosis regulation.

    abstract::Osteoarthritis (OA), primarily characterized by articular cartilage destruction, is the most common form of age-related degenerative whole-joint disease. No disease-modifying treatments for OA are currently available. Although OA is primarily characterized by cartilage destruction, our understanding of the processes c...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-18208-y

    authors: Park DR,Kim J,Kim GM,Lee H,Kim M,Hwang D,Lee H,Kim HS,Kim W,Park MC,Shim H,Lee SY

    更新日期:2020-08-28 00:00:00

  • Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome.

    abstract::Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations of the SLC26A4 gene, encoding pendrin, causes non-syndromic hearing loss with EVA or Pendred syndrome, a considerable number of patients appea...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15198-9

    authors: Li M,Nishio SY,Naruse C,Riddell M,Sapski S,Katsuno T,Hikita T,Mizapourshafiyi F,Smith FM,Cooper LT,Lee MG,Asano M,Boettger T,Krueger M,Wietelmann A,Graumann J,Day BW,Boyd AW,Offermanns S,Kitajiri SI,Usami SI,Nak

    更新日期:2020-03-12 00:00:00

  • Influence of atomic site-specific strain on catalytic activity of supported nanoparticles.

    abstract::Heterogeneous catalysis is an enabling technology that utilises transition metal nanoparticles (NPs) supported on oxides to promote chemical reactions. Structural mismatch at the NP-support interface generates lattice strain that could affect catalytic properties. However, detailed knowledge about strain in supported ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-05055-1

    authors: Nilsson Pingel T,Jørgensen M,Yankovich AB,Grönbeck H,Olsson E

    更新日期:2018-07-13 00:00:00

  • Copper-catalyzed enantioselective Sonogashira-type oxidative cross-coupling of unactivated C(sp3)-H bonds with alkynes.

    abstract::Transition metal-catalyzed enantioselective Sonogashira-type oxidative C(sp3)-C(sp) coupling of unactivated C(sp3)-H bonds with terminal alkynes has remained a prominent challenge. The difficulties mainly stem from the regiocontrol in unactivated C(sp3)-H bond functionalization and the inhibition of readily occurring ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-13705-1

    authors: Zhang ZH,Dong XY,Du XY,Gu QS,Li ZL,Liu XY

    更新日期:2019-12-12 00:00:00

  • Neural dynamics of the attentional blink revealed by encoding orientation selectivity during rapid visual presentation.

    abstract::The human brain is inherently limited in the information it can make consciously accessible. When people monitor a rapid stream of visual items for two targets, they typically fail to see the second target if it occurs within 200-500 ms of the first, a phenomenon called the attentional blink (AB). The neural basis for...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-14107-z

    authors: Tang MF,Ford L,Arabzadeh E,Enns JT,Visser TAW,Mattingley JB

    更新日期:2020-01-23 00:00:00

  • Mechanical evidence that Australopithecus sediba was limited in its ability to eat hard foods.

    abstract::Australopithecus sediba has been hypothesized to be a close relative of the genus Homo. Here we show that MH1, the type specimen of A. sediba, was not optimized to produce high molar bite force and appears to have been limited in its ability to consume foods that were mechanically challenging to eat. Dental microwear ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms10596

    authors: Ledogar JA,Smith AL,Benazzi S,Weber GW,Spencer MA,Carlson KB,McNulty KP,Dechow PC,Grosse IR,Ross CF,Richmond BG,Wright BW,Wang Q,Byron C,Carlson KJ,de Ruiter DJ,Berger LR,Tamvada K,Pryor LC,Berthaume MA,Strait DS

    更新日期:2016-02-08 00:00:00

  • Molecular structure of promoter-bound yeast TFIID.

    abstract::Transcription preinitiation complex assembly on the promoters of protein encoding genes is nucleated in vivo by TFIID composed of the TATA-box Binding Protein (TBP) and 13 TBP-associate factors (Tafs) providing regulatory and chromatin binding functions. Here we present the cryo-electron microscopy structure of promot...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07096-y

    authors: Kolesnikova O,Ben-Shem A,Luo J,Ranish J,Schultz P,Papai G

    更新日期:2018-11-07 00:00:00

  • EPR-aided approach for solution structure determination of large RNAs or protein-RNA complexes.

    abstract::High-resolution structural information on RNA and its functionally important complexes with proteins is dramatically underrepresented compared with proteins but is urgently needed for understanding cellular processes at the molecular and atomic level. Here we present an EPR-based protocol to help solving large RNA and...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4669

    authors: Duss O,Yulikov M,Jeschke G,Allain FH

    更新日期:2014-05-14 00:00:00

  • Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β2-adrenoceptor clusters assembled by alpha-actinin-4.

    abstract::Neisseria meningitidis (meningococcus) is an invasive bacterial pathogen that colonizes human vessels, causing thrombotic lesions and meningitis. Establishment of tight interactions with endothelial cells is crucial for meningococci to resist haemodynamic forces. Two endothelial receptors, CD147 and the β2-adrenergic ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms15764

    authors: Maïssa N,Covarelli V,Janel S,Durel B,Simpson N,Bernard SC,Pardo-Lopez L,Bouzinba-Ségard H,Faure C,Scott MGH,Coureuil M,Morand PC,Lafont F,Nassif X,Marullo S,Bourdoulous S

    更新日期:2017-06-01 00:00:00

  • Oscillatory surface rheotaxis of swimming E. coli bacteria.

    abstract::Bacterial contamination of biological channels, catheters or water resources is a major threat to public health, which can be amplified by the ability of bacteria to swim upstream. The mechanisms of this 'rheotaxis', the reorientation with respect to flow gradients, are still poorly understood. Here, we follow individ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-11360-0

    authors: Mathijssen AJTM,Figueroa-Morales N,Junot G,Clément É,Lindner A,Zöttl A

    更新日期:2019-07-31 00:00:00

  • Mapping ecologically relevant social behaviours by gene knockout in wild mice.

    abstract::The laboratory mouse serves as an important model system for studying gene, brain and behavioural interactions. Powerful methods of gene targeting have helped to decipher gene-function associations in human diseases. Yet, the laboratory mouse, obtained after decades of human-driven artificial selection, inbreeding, an...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5569

    authors: Chalfin L,Dayan M,Levy DR,Austad SN,Miller RA,Iraqi FA,Dulac C,Kimchi T

    更新日期:2014-08-05 00:00:00

  • An in-silico approach to predict and exploit synthetic lethality in cancer metabolism.

    abstract::Synthetic lethality is a promising concept in cancer research, potentially opening new possibilities for the development of more effective and selective treatments. Here, we present a computational method to predict and exploit synthetic lethality in cancer metabolism. Our approach relies on the concept of genetic min...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-00555-y

    authors: Apaolaza I,San José-Eneriz E,Tobalina L,Miranda E,Garate L,Agirre X,Prósper F,Planes FJ

    更新日期:2017-09-06 00:00:00

  • BORDER proteins protect expression of neighboring genes by promoting 3' Pol II pausing in plants.

    abstract::Ensuring that one gene's transcription does not inappropriately affect the expression of its neighbors is a fundamental challenge to gene regulation in a genomic context. In plants, which lack homologs of animal insulator proteins, the mechanisms that prevent transcriptional interference are not well understood. Here ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-12328-w

    authors: Yu X,Martin PGP,Michaels SD

    更新日期:2019-09-25 00:00:00

  • The energy cost of polypeptide knot formation and its folding consequences.

    abstract::Knots are natural topologies of chains. Yet, little is known about spontaneous knot formation in a polypeptide chain-an event that can potentially impair its folding-and about the effect of a knot on the stability and folding kinetics of a protein. Here we used optical tweezers to show that the free energy cost to for...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01691-1

    authors: Bustamante A,Sotelo-Campos J,Guerra DG,Floor M,Wilson CAM,Bustamante C,Báez M

    更新日期:2017-11-17 00:00:00

  • Systemic nanoparticle delivery of CRISPR-Cas9 ribonucleoproteins for effective tissue specific genome editing.

    abstract::CRISPR-Cas9 has emerged as a powerful technology that relies on Cas9/sgRNA ribonucleoprotein complexes (RNPs) to target and edit DNA. However, many therapeutic targets cannot currently be accessed due to the lack of carriers that can deliver RNPs systemically. Here, we report a generalizable methodology that allows en...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-17029-3

    authors: Wei T,Cheng Q,Min YL,Olson EN,Siegwart DJ

    更新日期:2020-06-26 00:00:00

  • Electron cascade for distant spin readout.

    abstract::The spin of a single electron in a semiconductor quantum dot provides a well-controlled and long-lived qubit implementation. The electron charge in turn allows control of the position of individual electrons in a quantum dot array, and enables charge sensors to probe the charge configuration. Here we show that the Cou...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-20388-6

    authors: van Diepen CJ,Hsiao TK,Mukhopadhyay U,Reichl C,Wegscheider W,Vandersypen LMK

    更新日期:2021-01-04 00:00:00

  • A bioreducible N-oxide-based probe for photoacoustic imaging of hypoxia.

    abstract::Hypoxia occurs when limited oxygen supply impairs physiological functions and is a pathological hallmark of many diseases including cancer and ischemia. Thus, detection of hypoxia can guide treatment planning and serve as a predictor of patient prognosis. Unfortunately, current methods suffer from invasiveness, poor r...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01951-0

    authors: Knox HJ,Hedhli J,Kim TW,Khalili K,Dobrucki LW,Chan J

    更新日期:2017-11-27 00:00:00

  • A transposable element insertion is associated with an alternative life history strategy.

    abstract::Tradeoffs affect resource allocation during development and result in fitness consequences that drive the evolution of life history strategies. Yet despite their importance, we know little about the mechanisms underlying life history tradeoffs. Many species of Colias butterflies exhibit an alternative life history str...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-13596-2

    authors: Woronik A,Tunström K,Perry MW,Neethiraj R,Stefanescu C,Celorio-Mancera MP,Brattström O,Hill J,Lehmann P,Käkelä R,Wheat CW

    更新日期:2019-12-17 00:00:00

  • Designer patterned functional fibers via direct imprinting in thermal drawing.

    abstract::Creating micro/nanostructures on fibers is beneficial for extending the application range of fiber-based devices. To achieve this using thermal fiber drawing is particularly important for the mass production of longitudinally uniform fibers up to tens of kilometers. However, the current thermal fiber drawing technique...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-17674-8

    authors: Wang Z,Wu T,Wang Z,Zhang T,Chen M,Zhang J,Liu L,Qi M,Zhang Q,Yang J,Liu W,Chen H,Luo Y,Wei L

    更新日期:2020-07-31 00:00:00

  • Mapping the dynamics and nanoscale organization of synaptic adhesion proteins using monomeric streptavidin.

    abstract::The advent of super-resolution imaging (SRI) has created a need for optimized labelling strategies. We present a new method relying on fluorophore-conjugated monomeric streptavidin (mSA) to label membrane proteins carrying a short, enzymatically biotinylated tag, compatible with SRI techniques including uPAINT, STED a...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms10773

    authors: Chamma I,Letellier M,Butler C,Tessier B,Lim KH,Gauthereau I,Choquet D,Sibarita JB,Park S,Sainlos M,Thoumine O

    更新日期:2016-03-16 00:00:00

  • The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice.

    abstract::Post-translational protein modifications are systems designed to expand restricted genomic information through functional conversion of target molecules. Ubiquitin-like post-translational modifiers regulate numerous cellular events through their covalent linkages to target protein(s) by an enzymatic cascade analogous ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms1182

    authors: Tatsumi K,Yamamoto-Mukai H,Shimizu R,Waguri S,Sou YS,Sakamoto A,Taya C,Shitara H,Hara T,Chung CH,Tanaka K,Yamamoto M,Komatsu M

    更新日期:2011-02-08 00:00:00