Abstract：
:Antibody humanization is a key step in the preclinical phase of the development of therapeutic antibodies, originally developed and tested in non-human models (most typically, in mouse). The standard technique of Complementarity-Determining Regions (CDR) grafting into human Framework Regions of germline sequences has some important drawbacks, in that the resulting sequences often need further back-mutations to ensure functionality and/or stability. Here we propose a new method to characterize the statistical distribution of the sequences of the variable regions of human antibodies, that takes into account phenotypical correlations between pairs of residues, both within and between chains. We define a "humanness score" of a sequence, comparing its performance in distinguishing human from murine sequences, with that of some alternative scores in the literature. We also compare the score with the experimental immunogenicity of clinically used antibodies. Finally, we use the humanness score as an optimization function and perform a search in the sequence space, starting from different murine sequences and keeping the CDR regions unchanged. Our results show that our humanness score outperforms other methods in sequence classification, and the optimization protocol is able to generate humanized sequences that are recognized as human by standard homology modelling tools.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Clavero-Álvarez A,Di Mambro T,Perez-Gaviro S,Magnani M,Bruscolini Pdoi
10.1038/s41598-018-32986-ysubject
Has Abstractpub_date
2018-10-04 00:00:00pages
14820issue
1issn
2045-2322pii
10.1038/s41598-018-32986-yjournal_volume
8pub_type
杂志文章abstract：:Bringing oxygen atoms from infinite, passing equilibrium until short enough distances, we aim to reveal the 4f5d electron bonding property and its relevance to the peculiar physical properties within PrO2 based on both accounting for electron Coulomb repulsion and spin-orbit coupling effects in combination with Wannie...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-34336-4
更新日期：2018-10-30 00:00:00
abstract：:Appropriate isolation methods are essential for unravelling the relative contribution of extracellular vesicles (EVs) and the EV-free secretome to homeostasis and disease. We hypothesized that ultrafiltration followed by size exclusion chromatography (UF-SEC) provides well-matched concentrates of EVs and free secreted...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-15717-7
更新日期：2017-11-10 00:00:00
abstract：:This study aimed to evaluate the effects of ischemia-reperfusion injury (IRI) on the risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation. Data of 195 patients were retrospectively analysed. Post-reperfusion aspartate (AST), alanine transaminase, and lactate dehydrogenase (LDH) levels were the...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-27319-y
更新日期：2018-06-12 00:00:00
abstract：:Knowledge about a tool's dynamics can be acquired from the visual configuration of the tool and through physical interaction. Here, we examine how visual information affects the generalization of dynamic learning during tool use. Subjects rotated a virtual hammer-like object while we varied the object dynamics separat...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-39507-5
更新日期：2019-02-25 00:00:00
abstract：:Finding strategies to preserve quantum resources in open systems is nowadays a main requirement for reliable quantum-enhanced technologies. We address this issue by considering structured cavities embedding qubits driven by a control technique known as frequency modulation. We first study a single qubit in a lossy cav...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-32661-2
更新日期：2018-09-24 00:00:00
abstract：:Fitness-related costs of evolving insecticide resistance have been reported in a number of insect species, but the interplay between evolutionary adaptation to insecticide pressure and variable environmental conditions has received little attention. We provisioned nymphs from three German cockroach (Blattella germanic...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep28731
更新日期：2016-06-27 00:00:00
abstract：:Most large carnivore populations currently occur in heterogeneous landscapes, with source populations embedded in a matrix of human-dominated habitats. Understanding changes in distribution of endangered carnivores is critical for prioritizing and implementing conservation strategies. We examined distribution and dyna...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-39293-0
更新日期：2019-02-28 00:00:00
abstract：:Organic gases undergoing conversion to form secondary organic aerosol (SOA) during atmospheric aging are largely unidentified, particularly in regions influenced by anthropogenic emissions. SOA dominates the atmospheric organic aerosol burden and this knowledge gap contributes to uncertainties in aerosol effects on cl...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep27881
更新日期：2016-06-17 00:00:00
abstract：:Microalgae have great potential for the production of biofuels due to the ability of the organism to accumulate large quantities of storage lipids under stress conditions. Mitogen activated protein kinase (MAPK) signaling cascades are widely recognized for their role in stress response signal transduction in eukaryote...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-32216-5
更新日期：2018-09-14 00:00:00
abstract：:At the basis of a trophic web, coprophagous animals like dung beetles (Scarabaeoidea) utilize resources that may have advantages (easy gain and handling) as well as drawbacks (formerly processed food). Several studies have characterized the nutrients, e.g. C/N ratios and organic matter content, for specific types of d...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-12265-y
更新日期：2017-09-22 00:00:00
abstract：:The secreted frizzled-related protein 5 gene (SFRP5) that antagonize the Wnt/β-catenin signaling is frequently inactivated by promoter methylation and oncogenic activation of the Wnt signaling pathway is common in many cancers. The curcumin-rich Curcuma longa has been reported to potent anti-cancer property involved i...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-53509-3
更新日期：2019-11-21 00:00:00
abstract：:Receptor-mediated endocytosis is an essential process in signalling pathways for activation of intracellular signalling cascades. One example is the Wnt signalling pathway that seems to depend on endocytosis of the ligand-receptor complex for initiation of Wnt signal transduction. To date, the roles of different endoc...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-49082-4
更新日期：2019-09-10 00:00:00
abstract：:Epigenetic deregulation, such as the reduction of histone acetylation levels, is thought to be causally linked to various maladies associated with aging. Consequently, histone deacetylase inhibitors are suggested to serve as epigenetic therapy by increasing histone acetylation. However, previous work suggests that man...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-22674-2
更新日期：2018-03-08 00:00:00
abstract：:Manual count of mitotic figures, which is determined in the tumor region with the highest mitotic activity, is a key parameter of most tumor grading schemes. It can be, however, strongly dependent on the area selection due to uneven mitotic figure distribution in the tumor section. We aimed to assess the question, how...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-73246-2
更新日期：2020-10-05 00:00:00
abstract：:Coupled networks are extremely fragile because a node failure of a network would trigger a cascade of failures on the entire system. Existing studies mainly focused on the cascading failures and the robustness of coupled networks when the networks suffer from attacks. In reality, it is necessary to recover the damaged...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep08439
更新日期：2015-02-13 00:00:00
abstract：:By moving the alkoxy group on the spacer from position 5 to position 4 to add another protocol for the algorithm for intermolecular and intramolecular hydrogen bonding interactions, highly regioselectivity of noncovalent synthesis of the hydrazide-based cyclic hexamers was achieved: one out of thirteen possible isomer...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep01059
更新日期：2013-01-01 00:00:00
abstract：:Alcohol consumption is one of the major causes of hepatic steatosis, fibrosis, cirrhosis, and superimposed hepatocellular carcinoma. Ethanol metabolism alters the NAD(+)/NADH ratio, thereby suppressing the activity of sirtuin family proteins, which may affect lipid metabolism in liver cells. However, it is not clear h...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep29352
更新日期：2016-07-11 00:00:00
abstract：:Cellular interactions can be modeled as complex dynamical systems represented by weighted graphs. The functionality of such networks, including measures of robustness, reliability, performance, and efficiency, are intrinsically tied to the topology and geometry of the underlying graph. Utilizing recently proposed geom...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep12323
更新日期：2015-07-14 00:00:00
abstract：:The intricate molecular processes underlying photosynthesis have long been studied using various analytic approaches. However, the three-dimensional (3D) dynamics of such photosynthetic processes remain unexplored due to technological limitations related to investigating intraorganellar mechanisms in vivo. By developi...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep29940
更新日期：2016-07-15 00:00:00
abstract：:Human aldose reductase (hAR, AKR1B1) has been explored as drug target since the 1980s for its implication in diabetic complications. An activated form of hAR was found in cells from diabetic patients, showing a reduced sensitivity to inhibitors in clinical trials, which may prevent its pharmacological use. Here we rep...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-39722-0
更新日期：2019-02-28 00:00:00
abstract：:The design, fabrication, and characterization of ultra-high responsivity photodetectors based on mesoscopic multilayer MoS2 is presented, which is a less explored system compared to direct band gap monolayer MoS2 that has received increasing attention in recent years. The device architecture is comprised of a metal-se...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-19367-1
更新日期：2018-01-19 00:00:00
abstract：ABSTARCT:Shape memory alloys (SMAs) have the ability to show large recoverable shape changes upon temperature, stress or magnetic field cycling. Their shape memory, material and magnetic properties (e.g. transformation temperatures, strain, saturation magnetization and strength) determine their prospects for applicatio...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-13434-9
更新日期：2017-11-01 00:00:00
abstract：:Variation of the magnitude of posterior alpha rhythm (8-12 Hz) has functional and behavioural effects in sensory processing and cognitive performances. Electrical brain activity, as revealed by electroencephalography (EEG), can be represented by a sequence of microstates of about 40-120 ms duration, in which distribut...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-58787-w
更新日期：2020-02-12 00:00:00
abstract：:Copy number variation (CNV) is a newly discovered form of intra-species genetic polymorphism that is defined as deletions or duplications of genome segments ranging from 1 kbp to several Mbp. CNV accounts for the majority of the genetic variation observed in humans (CNV regions cover more than 10% of the human genome)...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep31340
更新日期：2016-08-11 00:00:00
abstract：:The tunneled central venous catheter (CVC) plays an important role for hemodialysis patients, but CVC-related thrombosis in the central veins remain problematic. This study is the first try to numerically find out what hemodynamic parameters are predisposed to the initiation and formation of thrombus after CVC inserti...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-12456-7
更新日期：2017-11-21 00:00:00
abstract：:One quarter of individuals with Preserved Ratio Impaired Spirometry (PRISm) will develop airflow obstruction, but there are no established methods to identify these individuals. We examined the utility of FVC/TLC in identifying features of obstructive lung disease. The ratio of post-bronchodilator FVC and TLCCT from c...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-61932-0
更新日期：2020-03-20 00:00:00
abstract：:Accurate cancer diagnosis often requires extraction and purification of genetic materials from cells, and sophisticated instrumentations that follow. Otherwise in order to directly treat the diagnostic materials to cells, multiple steps to optimize dose concentration and treatment time are necessary due to diversity i...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep18497
更新日期：2015-12-18 00:00:00
abstract：:The human visual system has specialised mechanisms for encoding mirror-symmetry and for detecting symmetric motion-directions for objects that loom or recede from the observers. The contribution of motion to mirror-symmetry perception has never been investigated. Here we examine symmetry detection thresholds for stati...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep45679
更新日期：2017-04-04 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Scientific reports
pub_type： 已发布勘误
doi：10.1038/s41598-019-49306-7
更新日期：2019-09-03 00:00:00
abstract：:Antitumor drug development based on the concept of intervening in the antioxidant system of cancer cells has been gaining increased interest. In this study, we propose a promising strategy for cancer treatment using modulation of oxidative stress by suppression of glutathione S-transferases (GSTs), a typical antioxida...
journal_title：Scientific reports
pub_type： 杂志文章,收录出版
doi：10.1038/s41598-019-51462-9
更新日期：2019-10-14 00:00:00
