Biology subjects

Wang, Q.

Publications and source records attributed to Wang, Q..

At least 685 records · Page 38Linked to original sources

bioRxiv2020

Structural basis for repurposing a 100-years-old drug suramin for treating COVID-19

The COVID-19 pandemic by non-stop infections of SARS-CoV-2 has continued to ravage many countries worldwide. Here we report the discovery of suramin, a 100-year-old drug, as a potent inhibitor of the SARS-CoV-2 RNA dependent RNA polymerase (RdRp) through blocking the binding of RNA to the enzyme. In biochemical assays, suramin and its derivatives are at least 20-fold more potent than remdesivir, the currently approved nucleotide drug for COVID-19. The 2.6 [A] cryo-EM structure of the viral RdRp bound to suramin reveals two binding sites of suramin, with one site directly blocking the binding of the RNA template strand and the other site clash with the RNA primer strand near the RdRp catalytic active site, therefore inhibiting the viral RNA replication. Furthermore, suramin potently inhibits SARS-CoV-2 duplication in Vero E6 cells. These results provide a structural mechanism for the first non-nucleotide inhibitor of the SARS-CoV-2 RdRp and a rationale for repurposing suramin for treating COVID-19. One Sentence SummaryDiscovery and mechanism of suramin as potent SARS-CoV-2 RNA polymerase inhibitor and its repurposing for treating COVID-19.

molecular biology↗

bioRxiv2020

Automatic Recognition of Auditory Brainstem Response Characteristic Waveform based on BiLSTM

BackgroundAuditory brainstem response (ABR) test is widely used in newborn hearing screening and hearing disease diagnosis. Identifying and marking are challenging and repetitive tasks because of complex rules of ABR characteristic waveform and interference of background noise. MethodsThis study proposes an automatic method to recognize ABR characteristic waveform. First, binarization is created to mark 1024 sampling points accordingly. The selected characteristic area of ABR data is 0-8ms. The marking area is enlarged to expand feature information and reduce marking error. Second, a bi-directional long short-term memory (BiLSTM) network structure is established to improve relevance of sampling points, and an ABR sampling point classifier is obtained by training. Finally, mark points are obtained through thresholding. ResultsSpecific structure, related parameters, recognition effect, and noise resistance of network were explored in 614 sets of ABR clinical data, and recognition accuracy of waves I, III, and V can reach 92.91%. DiscussionThus, the proposed method can reduce the repetitive work of doctors and meet accuracy effectively. Therefore, this method has clinical potential.

bioinformatics↗

bioRxiv2020

Gait-symmetry-based human-in-the-loop optimization for unilateral transtibial amputees with robotic prostheses

Gait asymmetry due to the loss of unilateral limb increases the risk of injury or progressive joint degeneration. The development of wearable robotic devices paves a way to improve gait symmetry of unilateral amputees. Moreover, the state-of-the-art studies on human-in-the-loop optimization strategies through decreasing the metabolic cost as the optimization task, have met several challenges, e.g. too long period of optimization and the optimization feasibility for unilateral amputees who have the deficit of gait symmetry. Here, in this paper, we proposed gait-symmetry-based human-in-the-loop optimization method to decrease the risk of injury or progressive joint degeneration for unilateral transtibial amputees. The experimental results (N = 3 unilateral transtibial subjects) demonstrate that only average 9.0{+/-}4.1min of convergence was taken. Compared to gait symmetry while wearing prosthetics, after optimization, the gait symmetry indicator value of the subjects wearing the robotic prostheses was improved by 21.0% and meanwhile the net metabolic energy consumption value was reduced by 9.2%. Also, this paper explores the rationality of gait indicators and what kind of gait indicators are the optimization target. These results suggest that gait-symmetry-based human-in-the-loop strategy could pave a practical way to improve gait symmetry by accompanying the reduction of metabolic cost, and thus to decrease the risk of joint injury for the unilateral amputees.

bioengineering↗

bioRxiv2020

Chromosomes distribute randomly to, but not within, human neutrophil nuclear lobes

The proximity pattern and radial distribution of chromosome territories within spherical nuclei are well understood to be random and non-random, respectively. Whether this distribution pattern is conserved in the partitioned or lobed nuclei of polymorphonuclear cells is unclear. Here we use chromosome paint technology and a novel high-throughput imaging analysis pipeline to examine the chromosome territories of all 46 chromosomes in hundreds of single human neutrophils - an abundant and famously polymorphonuclear immune cell. By comparing the distribution of chromosomes to randomly shuffled controls, and validating with orthogonal chromosome conformation capture technology, we show for the first time that all human chromosomes randomly distribute to neutrophil nuclear lobes, while maintaining a non-random radial distribution within these lobes. Furthermore, by leveraging the power of this vast dataset, we are able to reveal characteristics of chromosome territories not detected previously. For example, we demonstrate that chromosome length correlates with three-dimensional volume not only in neutrophils but other human immune cells. This work demonstrates that chromosomes are largely passive passengers during the neutrophil lobing process, but are able to maintain their macro-level organisation within lobes. Furthermore, the random distribution of chromosomes to the naturally partitioned nuclear lobes suggests that specific transchromosomal interactions are unimportant in mature neutrophils.

immunology↗

bioRxiv2020

Cellular Anatomy of the Mouse Primary Motor Cortex

An essential step toward understanding brain function is to establish a cellular-resolution structural framework upon which multi-scale and multi-modal information spanning molecules, cells, circuits and systems can be integrated and interpreted. Here, through a collaborative effort from the Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based description of one brain structure - the primary motor cortex upper limb area (MOp-ul) of the mouse. Applying state-of-the-art labeling, imaging, computational, and neuroinformatics tools, we delineated the MOp-ul within the Mouse Brain 3D Common Coordinate Framework (CCF). We defined over two dozen MOp-ul projection neuron (PN) types by their anterograde targets; the spatial distribution of their somata defines 11 cortical sublayers, a significant refinement of the classic notion of cortical laminar organization. We further combine multiple complementary tracing methods (classic tract tracing, cell type-based anterograde, retrograde, and transsynaptic viral tracing, high-throughput BARseq, and complete single cell reconstruction) to systematically chart cell type-based MOp input-output streams. As PNs link distant brain regions at synapses as well as host cellular gene expression, our construction of a PN type resolution MOp-ul wiring diagram will facilitate an integrated analysis of motor control circuitry across the molecular, cellular, and systems levels. This work further provides a roadmap towards a cellular resolution description of mammalian brain architecture.

neuroscience↗

bioRxiv2020

Epithelial HVEM promotes basement membrane synthesis and intraepithelial T cell survival and migration

Intraepithelial T cells (IET) provide continuous surveillance of the intestinal epithelium, but little was known about how epithelial-derived signals regulate the IET population. We show that epithelial expression of the herpes virus entry mediator (HVEM), a member of the TNF receptor superfamily (TNFRSF), maintained the survival of small intestine IET, especially innate-like TCR{beta}+ cells lacking CD4 and CD8{beta}. Patrolling movement of all CD8+ IET also was impaired in the absence of HVEM. HVEM-deficient epithelial cells exhibited downregulation of synthesis of basement membrane components, including collagen IV. Collagen IV supported IET survival in vitro via interactions with {beta}1 integrins expressed by the IET; absence of {beta}1 integrins decreased some IET subsets. Therefore, these data define a circuit whereby epithelial cells regulate intestine resident T lymphocyte populations through basement membrane synthesis.

immunology↗

bioRxiv2020

Prime-boost vaccination of mice and Rhesus macaques with two novel adenovirus vectored COVID-19 vaccine candidates

COVID-19 vaccines are being developed urgently worldwide, among which single-shot adenovirus vectored vaccines represent a major approach. Here, we constructed two novel adenovirus vectored COVID-19 vaccine candidates on simian adenovirus serotype 23 (Sad23L) and human adenovirus serotype 49 vectors (Ad49L) carrying the full-length gene of SARS-CoV-2 spike protein (S), designated Sad23L-nCoV-S and Ad49L-nCoV-S vaccines, respectively. The immunogenicity elicited by these two vaccine strains was individually evaluated in mice. Specific humoral and cellular immune responses were proportionally observed in a dose-dependent manner, and stronger response was obtained by boosting. Furthermore, five rhesus macaques were intramuscularly injected with a dose of 5x109 PFU Sad23L-nCoV-S vaccine for prime vaccination, followed by boosting with 5x109 PFU of Ad49L-nCoV-S vaccine at 4-week interval. Three macaques were injected with Sad23L-GFP and Ad49L-GFP vectorial viruses as negative controls. Both mice and macaques tolerated well the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost vaccination regimen induced high titers of 103.16 S-binding antibody (S-BAb), 102.75 cell receptor binding domain (RBD)-BAb and 102.38 neutralizing antibody (NAb) to pseudovirus a week after boosting injection, followed by sustained high levels over 10 weeks of observation. Robust IFN-{gamma} secreting T-cell response (712.6 SFCs/106 cells), IL-2 secreting T-cell response (334 SFCs/106 cells) and intracellular IFN-{gamma} expressing CD4+/CD8+ T cell response (0.39%/0.55%) to S peptides were detected in the vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S vaccines can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials.

immunology↗

bioRxiv2020

CARD8 inflammasome mediates pyroptosis of HIV-1-infected cells by sensing viral protease activity

HIV-1 has high mutation rates and exists as mutant swarms in the host. Rapid evolution of HIV-1 allows the virus to outpace host immune system, leading to viral persistence. Novel approaches to target immutable components are needed to clear HIV-1 infection. Here we report a pattern-recognition receptor CARD8 that senses enzymatic activity of the HIV-1 protease, which is indispensable for the virus. All subtypes of HIV-1 can be sensed by CARD8 despite substantial viral diversity. HIV-1 evades CARD8 sensing because the viral protease remains inactive in infected cells prior to viral budding. Induction of premature intracellular activation of the viral protease triggers CARD8 inflammasome-mediated pyroptosis of HIV-1-infected cells. This strategy leads to clearance of latent HIV-1 in patient CD4+ T cells after virus reactivation. Taken together, our study identifies CARD8 as an inflammasome sensor of HIV-1 that holds promise as a strategy for clearance of persistent HIV-1 infection.

immunology↗

bioRxiv2020

S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates

SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-levels of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important new platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.

immunology↗

bioRxiv2020

Potent activation of SARM1 by NMN analogue VMN underlies vacor neurotoxicity

Axon loss underlies symptom onset and progression in many neurodegenerative disorders. Axon degeneration in injury and disease is promoted by activation of the nicotinamide adenine dinucleotide (NAD)-consuming enzyme SARM1 (sterile alpha and TIR motif-containing protein 1). Here, we report vacor mononucleotide (VMN), a metabolite of the pesticide and neurotoxin vacor, as the most potent yet SARM1 activator. Removal of SARM1 shows complete rescue from vacor-induced neuron and axon death in vitro and in vivo. We present the crystal structure of VMN bound to the Drosophila SARM1 regulatory armadillo-repeat domain, thus facilitating drug development to prevent SARM1 activation in human disease. This study indicates the likely mechanism of action of vacor as a pesticide and lethal neurotoxin in humans, provides important new tools for drug discovery, and further demonstrates that SARM1 removal can permanently block programmed axon death specifically induced by toxicity as well as genetic mutation.

neuroscience↗

bioRxiv2020

ERWR: Predicting Efficacious Drug Combinations in Cancer Based on Random Walk with Restart

(1) BackgroundCompared with monotherapy, efficacious drug combinations can increase the therapeutic effect, decrease drug resistance of experimental subjects and the side effects of drugs. Therefore, efficacious drug combinations are widely used in the treatment of complex diseases, such as various cancers. However, compared with the mathematical model and computational method, experimental screening efficacious drug combinations is time-consuming, costly, laborious, and inefficient; (2) Methodswe predicted efficacious drug combinations in cancer based on random walk with restart (RWRDC). An efficacious score can be obtained between any two individual drugs by RWRDC; (3) ResultsAs a result, we analyzed the rationality of the efficacious score first. Besides, compared with the other methods by leave-one-out cross-validation, all the Area Under Receiver Operating Characteristic Curves (AUROCs) of RWRDC were higher for data sets of breast cancer, colorectal cancer, and lung cancer. Moreover, the case study of breast cancer showed that RWRDC could discover potential efficacious drug combinations; (4) ConclusionsThese results suggest that RWRDC is a novel way to discover efficacious drug combinations in cancer, which provides new prospects for cancer treatment. Furthermore, RWRDC is a semi-supervised learning framework that can be used to predict combinations of drugs for other complex diseases.

bioinformatics↗

bioRxiv2020

Free ammonia pretreatment for anaerobic sludge digestion reduces the spread of antibiotic resistance

Sludge from the wastewater treatment plants (WWTPs) has been recognized as a reservoir of antibiotic resistance genes (ARGs). Free ammonia (FA, i.e. NH3-N) pretreatment has been demonstrated to be able to enhance anaerobic digestion, which is a widely used method for sludge treatment. However, the effect of combined FA pretreatment and anaerobic digestion on the fate of ARGs is still unknown. This study demonstrated for the first time that combined FA pretreatment (420 mg NH3-N/L for 24 h) and anaerobic digestion could reduce the abundances of the tested ARGs by 0.06 log10 gene copies/g TS (total solids) compared with the anaerobic digestion alone. Specifically, the experimental results showed that combined FA pretreatment and anaerobic digestion reduced the abundances of aac(6)-Ib-cr, blaTEM, sul2, tetA, tetB and tetX by 0.07, 0.37, 0.09, 0.32, 0.24 and 0.59 log10 gene copies/g TS compared with anaerobic digestion alone. In contrast, combined FA pretreatment and anaerobic digestion slightly increased the abundance of tetG by 0.05 log10 gene copies/g TS compared with anaerobic digestion alone. In addition, FA pretreatment did not significantly affect the abundance of sul1 and tetM during anaerobic digestion. This study revealed that FA pretreatment for anaerobic digestion could potentially reduce the spread of antibiotic resistance from the sludge to soil (while agriculture reuse is used as the sludge disposal method), thereby protecting the environment and human health.

bioengineering↗

bioRxiv2020

Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat due to the lack of effective drugs or vaccines against SARS-CoV-2. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a relatively new antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry into host cells, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and SARS-CoV-2-infected Ad-ACE2-transduced Tmprss2 knockout (Tmprss2-KO) and wild-type (WT) mice. TMPRSS2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cancer cells (LNCaP) but not in human lung cancer cells or patient-derived lung organoids. Although Tmprss2 knockout effectively blocked SARS-CoV-2 infection in ACE2-transduced mice, enzalutamide showed no antiviral activity due to the AR independence of TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19.

microbiology↗

bioRxiv2020

Inhibition of guanosine monophosphate synthetase (GMPS) blocks glutamine metabolism and prostate cancer growth in vitro and in vivo

Cancer cells increase their uptake of nutrients and metabolize them to provide the necessary building blocks for new cancer cells. Glutamine is a critical nutrient in cancer, however its contribution to purine metabolism in prostate cancer has not previously been determined. Guanosine monophosphate synthetase (GMPS) acts in the de novo purine biosynthesis pathway, utilizing a glutamine amide to synthesize the guanine nucleotide and replenish the purine pool in proliferative cancer cells. This study demonstrates that GMPS mRNA expression correlates with Gleason score in prostate cancer samples, while high GMPS expression was associated with decreased rates of overall and disease/progression-free survival. Pharmacological inhibition or knockdown of GMPS significantly decreased cell growth in both LNCaP and PC-3 prostate cancer cells. GMPS knockdown was rescued by addition of extracellular guanosine to the media, suggesting a direct effect on nucleotide synthesis. We utilized 15N-(amide)-glutamine and U-13C5-glutamine metabolomics to dissect the pathways involved, and intriguingly, despite similar growth inhibition by GMPS knockdown, we show unique metabolic effects across each cell line. PC-3 cells showed a build-up of purine precursors, as well as activation of purine salvage pathways highlighted by significant increases in guanine, adenosine, inosine and cytosine. Both cell lines exhibited increased levels of pyrimidines and prioritized TCA cycle in distinct ways to produce increased aspartate, another important purine precursor. Using a PC-3 xenograft mouse model, tumor growth was also significantly decreased after GMPS knockdown. These data further highlight the importance of glutamine metabolism for prostate cancer cell growth and provide support for GMPS as a new therapeutic target in prostate cancer.

cancer biology↗

bioRxiv2020

Micro-XRF study of the troodontid dinosaur Jianianhualong tengi reveals new biological and taphonomical signals

Jianianhualong tengi is a key taxon for understanding the evolution of pennaceous feathers as well as troodontid theropods, and it is known by only the holotype, which was recovered from the Lower Cretaceous Yixian Formation of western Liaoning, China. Here, we carried out a large-area micro-X-Ray fluorescence (micro-XRF) analysis on the holotypic specimen of Jianianhualong tengi via a Brucker M6 Jetstream mobile XRF scanner. The elemental distribution measurements of the specimen show an enrichment of typical bones couponing elements such as S, P and Ca allowing to visualize the fossil structure. Additionally, to this, the bones are enriched in several heavier elements such as Sr, Th, Y and Ce over the surrounding rocks. The enrichment is most likely associated to secondary mineralization and the phosphates from the bones. Interestingly the plumage shape correlates with an enrichment in elements such as Cu, Ni and Ti, consistent with a previous study [1] on Archaeopteryx using synchrotron imaging. The analysis presented here provide new biological and taphonomic information of this fossil. An in-situ and nondestructive micro-XRF analysis is currently the most ideal way to map the chemistry of fossils, so far this is manly restricted to small samples. Larger samples usually required a synchrotron facility for analysis. Our study demonstrated that laboratory-based large-area micro-XRF scanner can provides a practical tool for the study of large large-sized specimens allowing collect full chemical data for a better understanding of evolutionary and taphonomic processes.

paleontology↗

bioRxiv2020

Dispatched conformational dynamics couples transmembrane Na+ flux to release of lipid-modified Hedgehog signal

The DISP1 protein, related to the NPC1 and PTCH1 cholesterol transporters and to H+-driven transporters of the RND family, enables tissue patterning activity of the lipid-modified Hedgehog protein by releasing it from tightly-localized sites of embryonic expression. A 2.5 [A] resolution cryo-EM structure of DISP1 revealed three Na+ ions coordinated within a channel that traverses its transmembrane domain. This channel and Na+-binding are disrupted in DISP1-NNN (3.4 [A] resolution), a variant with isosteric substitutions for three intramembrane aspartates that each coordinate and neutralize charge for one of the three Na+ ions. DISP1-NNN and other variants that singly disrupt the Na+ sites retain binding to the lipid-modified Hedgehog protein, but most fail to export Hedgehog. The Sonic hedgehog signal (ShhN) interacts with the DISP1 extracellular domains (2.7 [A] complex structure), including an unusual extended DISP1 arm, at a location well above the membrane. Variability analysis reveals a dynamic series of DISP1 conformations, only a restricted subset of which appear to bind ShhN. The bound and unbound DISP1 conformations display distinct Na+ site occupancies; these differences, in conjunction with the unusual locations of certain lipids bound to DISP1, suggest a mechanism by which transmembrane Na+ flux may power extraction of the lipid-linked Hedgehog signal from the membrane, thus enabling its tissue patterning activity. The Na+-coordinating residues resolved in our DISP1 structures are wholly or partly conserved in some of the other metazoan RND family members, such as PTCH1 and NPC1, suggesting the utilization of Na+ flux to power their conformationally-driven activities.

biophysics↗

bioRxiv2020

Comment on Rapid and efficient in vivo astrocyte-to-neuron conversion with regional identity and connectivity?

Regenerating functional new neurons in the adult mammalian central nervous system (CNS) has been proven to be very challenging due to the inability of neurons to divide and repopulate themselves after neuronal loss. In contrast, glial cells in the CNS can divide and repopulate themselves under injury or disease conditions. Therefore, many groups around the world have been able to utilize internal glial cells to directly convert them into neurons for neural repair. We have previously demonstrated that ectopic expression of NeuroD1 in dividing glial cells can directly convert reactive glial cells into neurons. However, Wang et al. recently posted an article in bioRxiv challenging the entire field of in vivo glia-to-neuron conversion after using one single highly toxic dose of AAV (2x1013 gc/ml, 1 l) in the mouse cortex, producing artifacts that are very difficult to interpret. We present data here that reducing AAV dosage to safe level will avoid artifacts caused by toxic dosage. We also demonstrate with Aldh1l1-CreERT2 and Ai14 reporter mice that lineage-traced astrocytes can be successfully converted into NeuN+ neurons after infected by AAV5 GFAP::NeuroD1. Retroviral expression of NeuroD1 further confirms our previous findings that dividing glial cells can be converted into neurons. Together, the incidence of Wang et al. sends an alarming signal to the entire in vivo reprogramming field that the dosage of viral vectors is a critical factor to consider when designing proper experiments. For AAV, we recommend a relatively safe dose of 1x1010 - 1x1012 gc/ml (~1 l) in the rodent brain for cell conversion experiments addressing basic science questions. For therapeutic purpose under injury or diseased conditions, AAV dosage needs to be adjusted through a series of dose finding experiments. Moreover, we recommend that the AAV results are further verified with retroviruses that mainly express transgenes in dividing glial cells in order to draw solid conclusions.

neuroscience↗

bioRxiv2020

Antibody Upstream Sequences Diversity and Its Biological Implications Revealed by Repertoire Sequencing

The sequence upstream of antibody variable region (Antibody Upstream Sequence, or AUS) consists of 5 untranslated region (5 UTR) and two leader regions, L-PART1 and L-PART2. The sequence variations in AUS affect the efficiency of PCR amplification, mRNA translation, and subsequent PCR-based antibody quantification as well as antibody engineering. Despite their importance, the diversity of AUSs has long been neglected. Utilizing the rapid amplification of cDNA ends (5RACE) and high-throughput antibody repertoire sequencing (Rep-Seq) technique, we acquired full-length AUSs for human, rhesus macaque (RM), cynomolgus macaque (CM), mouse, and rat. We designed a bioinformatics pipeline and discovered 2,957 unique AUSs, corresponding to 2,786 and 1,159 unique sequences for 5 UTR and leader, respectively. Comparing with the leader records in the international ImMunoGeneTics (IMGT), while 529 were identical, 313 were with single nucleotide polymorphisms (SNPs), 280 were totally new, and 37 updated the incomplete records. The diversity of AUSs impact on related antibody biology was also probed. Taken together, our findings would facilitate Rep-Seq primer design for capturing antibodies comprehensively and efficiently as well as provide a valuable resource for antibody engineering and the studies of antibody at the molecular level.

bioinformatics↗