Computational Analysis of Pathogenetic Pathways in Alzheimer’s Disease and Prediction of Potential Therapeutic Drugs
Abstract
:1. Introduction
2. Materials and Methods
2.1. Dataset Selection and Analysis
2.2. In Silico Pharmacology
3. Results
3.1. Identification of the AD Gene Expression Profile
3.2. Prediction of Novel Chemotherapeutics for AD
3.3. Prediction of Drugs That May Predispose to AD
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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ID | fdr_pval | Pval | zval | Qval | Qpval | Gene_Name |
---|---|---|---|---|---|---|
40979 | 0.0029 | 4.9 × 10-6 | −4.6 | 0.74 | 0.39 | NA |
ABCC10 | 0.0029 | 5.9 × 10-6 | 4.5 | 0.22 | 0.64 | ATP-binding cassette subfamily C member 10 |
ARID3B | 0.0029 | 3.6 × 10-6 | 4.6 | 0.053 | 0.82 | AT-rich interaction domain 3B |
AVEN | 0.0029 | 7.2 × 10-6 | 4.5 | 0.015 | 0.9 | apoptosis and caspase activation inhibitor |
C17orf28 | 0.0029 | 4.1 × 10-6 | 4.6 | 0.014 | 0.91 | NA |
C18orf1 | 0.0029 | 2.4 × 10-6 | −4.7 | 0.06 | 0.81 | NA |
C9orf123 | 0.0029 | 3.1 × 10-6 | 4.7 | 0.049 | 0.82 | NA |
CALB1 | 0.0029 | 3 × 10-6 | −4.7 | 0.12 | 0.73 | calbindin 1 |
CASP9 | 0.0029 | 7.3 × 10-6 | 4.5 | 0.095 | 0.76 | caspase 9 |
CCDC74B | 0.0029 | 1.9 × 10-6 | −4.8 | 0.49 | 0.48 | coiled-coil domain containing 74B |
CD9 | 0.0029 | 5 × 10-6 | −4.6 | 0.078 | 0.78 | CD9 molecule |
CMTM7 | 0.0029 | 7.5 × 10-6 | −4.5 | 0.019 | 0.89 | CKLF-like MARVEL transmembrane domain containing 7 |
CNTNAP2 | 0.0029 | 2.2 × 10-6 | 4.7 | 0.000046 | 0.99 | contactin-associated protein-like 2 |
CUX2 | 0.0029 | 1.3 × 10-6 | −4.8 | 0.2 | 0.65 | cut-like homeobox 2 |
DNER | 0.0029 | 6.2 × 10-6 | −4.5 | 0.48 | 0.49 | delta/notch-like EGF repeat containing |
EBF3 | 0.0029 | 5.4 × 10-6 | 4.5 | 1 | 0.31 | early B cell factor 3 |
EDNRA | 0.0029 | 1.5 × 10-6 | −4.8 | 0.083 | 0.77 | endothelin receptor type A |
FEZ1 | 0.0029 | 7.5 × 10-6 | −4.5 | 0.014 | 0.9 | fasciculation and elongation protein zeta 1 |
FOXD1 | 0.0029 | 2.7 × 10-6 | 4.7 | 0.26 | 0.61 | forkhead box D1 |
GAS2L3 | 0.0029 | 8.1 × 10-6 | −4.5 | 0.16 | 0.69 | growth arrest specific 2 like 3 |
GRIK4 | 0.0029 | 5.8 × 10-6 | −4.5 | 0.0041 | 0.95 | glutamate ionotropic receptor kainate type subunit 4 |
GRIP1 | 0.0029 | 7.3 × 10-6 | −4.5 | 0.2 | 0.65 | glutamate receptor-interacting protein 1 |
GRM8 | 0.0029 | 6.5 × 10-6 | −4.5 | 0.5 | 0.48 | glutamate metabotropic receptor 8 |
HIST1H3F | 0.0029 | 6.4 × 10-6 | −4.5 | 0.00057 | 0.98 | histone cluster 1 H3 family member f |
HOXA5 | 0.0029 | 7.9 × 10-6 | −4.5 | 1.1 | 0.3 | homeobox A5 |
IGF2AS | 0.0029 | 1.8 × 10-6 | 4.8 | 0.02 | 0.89 | NA |
ISLR | 0.0029 | 3.9 × 10-6 | −4.6 | 0.17 | 0.68 | immunoglobulin superfamily containing leucine-rich repeat |
ITGA2 | 0.0029 | 4.7 × 10-6 | −4.6 | 0.34 | 0.56 | integrin subunit alpha 2 |
KAL1 | 0.0029 | 5.3 × 10-6 | 4.6 | 0.45 | 0.5 | NA |
KCNC4 | 0.0029 | 8 × 10-6 | 4.5 | 0.78 | 0.38 | potassium voltage-gated channel subfamily C member 4 |
KCNH2 | 0.0029 | 7.2 × 10-6 | −4.5 | 0.000082 | 0.99 | potassium voltage-gated channel subfamily H member 2 |
KIF20A | 0.0029 | 6.6 × 10-6 | −4.5 | 0.054 | 0.82 | kinesin family member 20A |
LEF1 | 0.0029 | 7 × 10-6 | −4.5 | 0.95 | 0.33 | lymphoid enhancer-binding factor 1 |
LHFPL3 | 0.0029 | 3.5 × 10-6 | −4.6 | 0.68 | 0.41 | LHFPL tetraspan subfamily member 3 |
LMO2 | 0.0029 | 7 × 10-6 | 4.5 | 0.65 | 0.42 | LIM domain only 2 |
LOX | 0.0029 | 5.1 × 10-6 | −4.6 | 0.075 | 0.78 | lysyl oxidase |
NEDD9 | 0.0029 | 1.8 × 10-6 | −4.8 | 0.0085 | 0.93 | neural precursor cell expressed, developmentally downregulated 9 |
NEK6 | 0.0029 | 6.3 × 10-6 | −4.5 | 0.011 | 0.92 | NIMA-related kinase 6 |
PPEF1 | 0.0029 | 6.7 × 10-6 | −4.5 | 0.057 | 0.81 | protein phosphatase with EF-hand domain 1 |
RAP1A | 0.0029 | 1.3 × 10-6 | 4.8 | 0.00039 | 0.98 | RAP1A, member of the RAS oncogene family |
RASL11B | 0.0029 | 8.2 × 10-6 | −4.5 | 0.017 | 0.9 | RAS-like family 11 member B |
RGS16 | 0.0029 | 1.5 × 10-6 | 4.8 | 0.01 | 0.92 | regulator of G protein signaling 16 |
RNF152 | 0.0029 | 6.9 × 10-6 | −4.5 | 0.47 | 0.49 | ring finger protein 152 |
RUNX1T1 | 0.0029 | 2.8 × 10-6 | 4.7 | 0.073 | 0.79 | RUNX1 translocation partner 1 |
SERPINF1 | 0.0029 | 3.1 × 10-6 | 4.7 | 0.05 | 0.82 | serpin family F member 1 |
SIK3 | 0.0029 | 3.1 × 10-6 | 4.7 | 0.25 | 0.62 | SIK family kinase 3 |
SLIT1 | 0.0029 | 5.7 × 10-6 | −4.5 | 0.0099 | 0.92 | slit guidance ligand 1 |
SLIT2 | 0.0029 | 2 × 10-6 | −4.8 | 0.02 | 0.89 | slit guidance ligand 2 |
TCEAL2 | 0.0029 | 5.8 × 10-6 | −4.5 | 0.067 | 0.8 | transcription elongation factor A like 2 |
TCTA | 0.0029 | 4.1 × 10-6 | 4.6 | 0.18 | 0.67 | T cell leukemia translocation altered |
ID | Cosine Similarity | FDR(BH) | BBB* |
---|---|---|---|
Naftifine | −0.18 | 0.01 | BBB- |
Moricizine | −0.18 | 0.02 | BBB- |
Ketoconazole | −0.18 | 0.02 | BBB+ |
Perindopril | −0.17 | 0.02 | BBB- |
Fexofenadine | −0.17 | 0.02 | BBB- |
Vecuronium | −0.17 | 0.03 | n.a. |
Mesoridazine | −0.16 | 0.02 | BBB+ |
Raltegravir | −0.16 | 0.03 | n.a. |
Sapropterin | −0.15 | 0.03 | n.a. |
Entacapone | −0.15 | 0.03 | BBB+ |
Etanercept | −0.15 | 0.03 | n.a. |
Trimipramine | −0.14 | 0.03 | BBB+ |
Trifluoperazine | −0.14 | 0.04 | BBB+ |
Itraconazole | −0.14 | 0.04 | BBB+ |
ID | Cosine Similarity | FDR(BH) | BBB |
---|---|---|---|
Irinotecan | 0.24 | 0.01 | BBB- |
Cyproheptadine | 0.22 | 0.01 | BBB+ |
Teniposide | 0.22 | 0.01 | BBB+ |
Phenoxybenzamine | 0.22 | 0.01 | BBB- |
Pitavastatin | 0.22 | 0.01 | n.a. |
Mitomycin | 0.21 | 0.01 | BBB- |
Etoposide | 0.21 | 0.01 | BBB- |
Busulfan | 0.19 | 0.02 | BBB+ |
Sorafenib | 0.18 | 0.01 | BBB+ |
Prazosin | 0.18 | 0.02 | BBB+ |
Fluocinolone acetonide | 0.18 | 0.02 | n.a. |
Dirithromycin | 0.17 | 0.01 | BBB- |
Bortezomib | 0.17 | 0.02 | n.a. |
Podofilox | 0.17 | 0.02 | n.a. |
Interferon alfa-n3 | 0.17 | 0.02 | n.a. |
Vinblastine | 0.17 | 0.03 | BBB+ |
Carbidopa | 0.16 | 0.02 | BBB- |
Pentobarbital | 0.16 | 0.02 | BBB+ |
Acetaminophen | 0.16 | 0.02 | n.a. |
Vincristine | 0.16 | 0.02 | BBB- |
Methoxsalen | 0.16 | 0.02 | BBB- |
Propranolol | 0.16 | 0.02 | BBB- |
Clofarabine | 0.16 | 0.02 | BBB- |
Gatifloxacin | 0.16 | 0.02 | BBB- |
Mebendazole | 0.16 | 0.03 | BBB- |
Benzonatate | 0.16 | 0.03 | BBB- |
Azacitidine | 0.16 | 0.03 | n.a. |
Dicloxacillin | 0.15 | 0.02 | BBB- |
Tenofovir disoproxil | 0.15 | 0.03 | n.a. |
Floxuridine | 0.15 | 0.03 | BBB- |
Miglitol | 0.15 | 0.03 | BBB- |
Diazoxide | 0.15 | 0.03 | BBB- |
Bupropion | 0.15 | 0.03 | BBB+ |
Dexrazoxane | 0.15 | 0.04 | BBB- |
Kanamycin | 0.15 | 0.04 | BBB- |
Montelukast | 0.14 | 0.03 | n.a. |
Nafcillin | 0.14 | 0.03 | BBB- |
Sunitinib | 0.14 | 0.03 | BBB+ |
Tramadol | 0.14 | 0.04 | BBB+ |
Cephalexin | 0.14 | 0.04 | BBB- |
Prednicarbate | 0.14 | 0.04 | BBB+ |
Clopidogrel | 0.13 | 0.03 | BBB- |
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Petralia, M.C.; Mangano, K.; Quattropani, M.C.; Lenzo, V.; Nicoletti, F.; Fagone, P. Computational Analysis of Pathogenetic Pathways in Alzheimer’s Disease and Prediction of Potential Therapeutic Drugs. Brain Sci. 2022, 12, 827. https://doi.org/10.3390/brainsci12070827
Petralia MC, Mangano K, Quattropani MC, Lenzo V, Nicoletti F, Fagone P. Computational Analysis of Pathogenetic Pathways in Alzheimer’s Disease and Prediction of Potential Therapeutic Drugs. Brain Sciences. 2022; 12(7):827. https://doi.org/10.3390/brainsci12070827
Chicago/Turabian StylePetralia, Maria Cristina, Katia Mangano, Maria Catena Quattropani, Vittorio Lenzo, Ferdinando Nicoletti, and Paolo Fagone. 2022. "Computational Analysis of Pathogenetic Pathways in Alzheimer’s Disease and Prediction of Potential Therapeutic Drugs" Brain Sciences 12, no. 7: 827. https://doi.org/10.3390/brainsci12070827
APA StylePetralia, M. C., Mangano, K., Quattropani, M. C., Lenzo, V., Nicoletti, F., & Fagone, P. (2022). Computational Analysis of Pathogenetic Pathways in Alzheimer’s Disease and Prediction of Potential Therapeutic Drugs. Brain Sciences, 12(7), 827. https://doi.org/10.3390/brainsci12070827