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Machine Learning Discoveries of AURKB-X Synergy in ETC-1922159 Treated Colorectal Cancer Cells

Submitted:

29 December 2024

Posted:

31 December 2024

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Abstract
Aurora kinase B (AURKB) is one of the components that make up a complex called the chromosome passenger complex (CPC). The major functions of AURKB are to regulate kinetochore-microtubule attachments as well as cytokinesis. In colorectal cancer (CRC) cells treated with ETC-1922159, AURKB was found to be down regulated along with other genes. A recently developed search engine ranked combinations of AURKB-X (X, a particular gene/protein) at 2nd order level after drug administration. Some of these combinations have been tested in wet lab, however many have been pointed out by the search engine that are yet to be explored/tested. These rankings re- veal which AURKB-X combinations might be working synergistically in CRC. In this research work, I cover combinations of AURKB with ZW10 interacting kinetochore protein (ZWINT/ZWINT-1), inner centromere protein (INCENP), targeting protein for xenopus kinesin-like protein 2 (TPX2), WNT pathway components, chromatin licens- ing and DNA replication factor 1 (CDT1), G2 and S-phase expressed 1 (GTSE1), vaccinia related kinase 1 (VRK1), RecQ like helicase 4 (RECQL4), histone H3 associated protein kinase (HASPIN/GSG2), centromere protein (CENP), E2F transcription factor (E2F), cell division cycle (CDC), ubiquitin specific peptidase (USP), Nucleoporin (NUP), gem nuclear organelle associated protein (GEMIN), mitotic arrest deficient 2 like (MAD2L), homeobox (HOX), DExH-box helicase (DHX), polo like kinase (PLK), budding uninhibited by benzimidazoles (BUB), DNA topoisomerase (TOP), cyclin dependent kinase (CDK), alkB homolog lysine demethylase (ALKBH), protein arginine methyltransferase (PRMT), shugoshin (SGO), spindle and kinetochore associated com- plex subunit (SKA), growth arrest specific (GAS) and kinesin family member (KIF) family.
Keywords: 
AURKB
;  
Porcupine inhibitor ETC-1922159
;  
sensitivity analysis
;  
colorectal cancer
Subject: 
Computer Science and Mathematics  -   Mathematical and Computational Biology

1. Introduction

1.1. Aurora Kinase

Aurora kinases (AURKs) regulate chromosome-microtubule attachments, centrosome duplication and separation, chromosome condensation, bipolar spindle assembly, the spindle checkpoint and cytokinesis (Zhang [1]). Drosophila aurora was first identified by Glover et al. [2] where mutations in aurora prevented centrosome separation. Comprehensive review on AURKs can be found in Carmena and Earnshaw [3] and Willems et al. [4]. Bischoff et al. [5] identified human homologue of drosophila aurora kinase which was amplified in human colorectal cancers. Further, Ota et al. [6] found increased phosphorylation of histone H3 for maintenance of proper chromosome dynamics during mitosis, due to AIM-1/AURKB overexpression, thus leading to chromosome instability. They also observe that there was increased expression of the AIM-1 gene in human colorectal tumors. Recently, the findings of overexpression of AURKB in colorectal cancer has been confirmed in Shah et al. [7] and Li et al. [8]. In this research, I focus on Aurora kinase B (AURKB). AURKB works in tandem with multiple components and some combinations of AURKB have been confrimed in wet lab. However, many of the combinations have not been explored/tested or are known. To reveal these combinations, I use a modification of a recently published machine learning based search engine, details of which are given in the next section.

1.2. Combinatorial Search Problem and a Possible Solution

In a recently published work Sinha [9], a frame work of a search engine was developed which can rank combinations of factors (genes/proteins) in a signaling pathway. Readers are requested to go through the adaptation of the above mentioned work for gaining deeper insight into the working of the pipeline and its use of published data set generated after administration of ETC-1922159, Sinha [10]. The work uses SVM package by Joachims [11] in https://www.cs.cornell.edu/people/tj/svm_light/svm_rank.html. I use the adaptation to rank 2nd order gene combinations.

2. Results & Discussion

2.1. AURKB Related Synergies

2.1.1. AURKB - ZWINT / INCENP / TPX2 / WNT Pathway Components / CDT1 / GTSE1 / VRK1 / RECQL4 / GSG2

Kasuboski et al. [12] identified Zwint-1 (ZWITN) as a novel Aurora B substrate required for regulation of the spindle assembly checkpoint. Abdul Azeez et al. [13] studied the structural mechanism of AURKB activation that binds to the C-terminal domain of INCENP (full activation of which requires phosphorylation of two serine residues of INCENP). TPX2 is a co-activator protein of AURKB which forms the core of the chromosomal passenger complex, as shown by Iyer and Tsai [14]. Luo et al. [15] demonstrate an atypical function of a centrosomal module in WNT signalling as WNT-PCP protein DVL2 (as studied in Luga et al. [16]) associated with CEP192-PLK4/AURKB complex. Agarwal et al. [17] provides mechanistic insight into how CDT1 stabilizes kinetochore–microtubule attachments via an AURKB phosphorylation. GTSE1 regulates AURKB activity via spindle microtubule dynamics, as shown by Tipton et al. [18]. Moura et al. [19] propose formation of a complex between VRK1 and AURKB in the phosphorylation of Histone H3 and progression of mitosis. Fang et al. [20] demonstrate that RECQL4 interacts with AURKB, thus forming an axis which is essential for cell cycle progression, cellular proliferation and mitotic integrity. Zhang and Huang [21] found that one of the factors for promotion of thyroid cancer was stabilization of AURKB by GSG2. All these combinations have been established in wet lab experiments and in colorectal cancer cells treated with ETC-1922159, these components taken individually and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these INDIVIDUAL member along with AURKB.
Table 1 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 2 generated from analysis of the ranks in Table 1. The Table 1 shows rankings of individual members w.r.t AURKB. ZWINT - AURKB shows low ranking of 1 (laplace) , 38 (linear) and 18 (rbf). INCENP - AURKB shows low ranking of 678 (laplace) , 941 (linear) and 571 (rbf). TPX2 - AURKB shows low ranking of 10 (laplace) , 10 (linear) , and (rbf). WNT10B - AURKB shows low ranking of 583 (laplace) , 491 (linear) and 578 (rbf). CDT1 - AURKB shows low ranking of 318 (laplace) , 135 (linear) and 290 (rbf). GTSE1 - AURKB shows low ranking of 537 (laplace) , 283 (linear) and 137 (rbf). VRK1 - AURKB shows low ranking of 181 (laplace) , 848 (linear) and 229 (rbf). RECQL4 - AURKB shows low ranking of 897 (laplace) , 439 (linear) and 508 (rbf). GSG2 - AURKB shows low ranking of 74 (laplace) , 189 (linear) and 375 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
One can also interpret the results of the Table 1 graphically, with the following influences - • INDIVIDUAL family w.r.t AURKB with AURKB − > ZWINT / INCENP / TPX2 / WNT10B / CDT1 / GTSE1 / VRK1 / RECQL4 / GSG2 .

2.1.2. AURKB - CENP

Kong et al. [22] demonstrate that CENPC-MIS12C interaction helps in recruiting AURKB, thus forming a regulatory loop which is important for chromosome segregation. Further, Liu et al. [23] show that AURKB phosphorylates CENPW thus enhancing the interaction between CENPW and CENPT to ensure chromosome segregation. In colorectal cancer cells treated with ETC-1922159, CENP family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these CENP member along with AURKB.
Table 3 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 4 generated from analysis of the ranks in Table 3. The Table 3 shows rankings of individual members w.r.t AURKB. CENPU - AURKB shows low ranking of 38 (laplace), 35 (linear) and 11 (rbf). CENPF - AURKB shows low ranking of 39 (laplace), 58 (linear) and 136 (rbf). CENPH - AURKB shows low ranking of 83 (laplace), 22 (linear) and 88 (rbf). CENPA - AURKB shows low ranking of 122 (laplace), 49 (linear) and 38 (rbf). CENPE - AURKB shows low ranking of 143 (laplace), 27 (linear) and 829 (rbf). CENPJ - AURKB shows low ranking of 164 (laplace), 113 (linear) and 592 (rbf). CENPW - AURKB shows low ranking of 217 (laplace), 241 (linear) and 512 (rbf). CENPK - AURKB shows low ranking of 232 (laplace), 276 (linear) and 49 (rbf). CENPI - AURKB shows low ranking of 368 (laplace), 521 (linear) and 65 (rbf). CENPN - AURKB shows low ranking of 546 (laplace), 906 (linear) and 366 (rbf). CENPM - AURKB shows low ranking of 713 (laplace), 414 (linear) and 858 (rbf). CENPL - AURKB shows low ranking of 748 (laplace), 1117 (linear) and 695 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, CENPO and CENPV showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 3 graphically, with the following influences - • CENP family w.r.t AURKB with AURKB − > CENP-U/F/H/A/E/J/W/K/I/N/M/L.

2.1.3. AURKB - E2F

In clear cell renal cell carcinoma (ccRCC), Li et al. [8] showed that AURKB/CDC37 complex promotes E2F1 release as one of the activity, which in turn activates AURKB transcription and forms a positive feedforward loop in ccRCC. In colorectal cancer cells treated with ETC-1922159, E2F family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these E2F member along with AURKB.
Table 5 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 6 generated from analysis of the ranks in Table 5. The Table 5 shows rankings of individual members w.r.t AURKB. E2F8 - AURKB shows low ranking of 95 (laplace), 252 (linear) and 125 (rbf). E2F1 - AURKB shows low ranking of 499 (laplace), 243 (linear) and 1086 (rbf). E2F7 - AURKB shows low ranking of 1034 (laplace), 777 (linear) and 313 (rbf). E2F2 - AURKB shows low ranking of 1057 (laplace), 1498 (linear) and 839 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, E2F5 showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 5 graphically, with the following influences - • E2F family w.r.t AURKB with AURKB − > E2F-8/1/7/2.

2.1.4. AURKB - CDC

As mentioned in the preceding section, Li et al. [8] identifified of CDC37 as a molecular chaperone for AURKB ehich is effective in formation of AURKB/E2F1-positive feedforward loop in ccRCC. In colorectal cancer cells treated with ETC-1922159, CDC family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these CDC member along with AURKB.
Table 7 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 8 generated from analysis of the ranks in Table 7. The Table 7 shows rankings of individual members w.r.t AURKB. CDC20 - AURKB shows low ranking of 60 (laplace), 48 (linear) and 260 (rbf). CDC7 - AURKB shows low ranking of 116 (laplace), 52 (linear) and 20 (rbf). CDC45 - AURKB shows low ranking of 157 (laplace), 50 (linear) and 111 (rbf). CDC25C - AURKB shows low ranking of 235 (laplace), 153 (linear) and 282 (rbf). CDC25A - AURKB shows low ranking of 340 (laplace), 364 (linear) and 798 (rbf). CDC6 - AURKB shows low ranking of 1080 (laplace), 708 (linear) and 1075 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, CDC23 and CDC123 showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 7 graphically, with the following influences - • CDC family w.r.t AURKB with AURKB − > CDC-20/7/45/25C/25A/6.

2.1.5. AURKB - USP

In gastric cancer, Tu et al. [24] showed that transcription factor FUBP1 activates USP29 gene transcription leading to stabilization of AURKB. In colorectal cancer cells treated with ETC-1922159, USP family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these USP member along with AURKB.
Table 9 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 10 generated from analysis of the ranks in Table 9. The Table 9 shows rankings of individual members w.r.t AURKB. USP13 - AURKB shows low ranking of 129 (laplace), 240 (linear) and 862 (rbf). USP28 - AURKB shows low ranking of 1082 (laplace), 798 (linear) and 935 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, USP10, USP1, USP36 and USP39 showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 9 graphically, with the following influences - • USP family w.r.t AURKB with AURKB − > USP-13/28.

2.1.6. AURKB - RANBP/NUP

Di Cesare et al. [25] found that RANBP2/NUP358 controlled the SUMOylation of AURKB in early mitosis. In colorectal cancer cells treated with ETC-1922159, RANBP/NUP family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these RANBP/NUP member along with AURKB.
Table 11 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 12 generated from analysis of the ranks in Table 11. The Table 11 shows rankings of individual members w.r.t AURKB. RANBP1 - AURKB shows low ranking of 448 (laplace), 1179 (linear) and 638 (rbf). NUP35 - AURKB shows low ranking of 761 (laplace), 421 (linear) and 34 (rbf). NUP155 - AURKB shows low ranking of 886 (laplace) and 1471 (linear). NUP210 - AURKB shows low ranking of 937 (laplace) and 520 (linear). NUP43 - AURKB shows low ranking of 1033 (laplace), 405 (linear) and 959 (rbf). NUP37 - AURKB shows low ranking of 1160 (laplace), 863 (linear) and 1346 (rbf). NUP160 - AURKB shows low ranking of 1181 (laplace), 742 (linear) and 1412 (rbf). NUP107 - AURKB shows low ranking of 1194 (laplace), 1527 (linear) and 883 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, RANBP17, NUP93, NUP133, NUP85, NUP88, NUP205, NUP54, NUP188 and NUP62 showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 11 graphically, with the following influences - • NUP family w.r.t AURKB with AURKB − > RANBP1 and AURKB − > NUP-35/155/210/43/37/160/107.

2.1.7. AURKB - GEMIN

Non small cell lung cancer progression occurs as GEMIN6 expression positively correlates with AURKB, as has been shown by Lin et al. [26]. In colorectal cancer cells treated with ETC-1922159, GEMIN family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these GEMIN member along with AURKB.
Table 13 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 14 generated from analysis of the ranks in Table 13. The Table 13 shows rankings of individual members w.r.t AURKB. GEMIN6 - AURKB shows low ranking of 367 (laplace), 971 (linear) and 523 (rbf). GEMIN5 - AURKB shows low ranking of 595 (laplace), 841 (linear) and 345 (rbf). GEMIN2 - AURKB shows low ranking of 954 (laplace) and 687 (linear). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, GEMIN4 and GEMIN7 showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 13 graphically, with the following influences - • GEMIN family w.r.t AURKB with AURKB − > GEMIN-6/5/2.

2.1.8. AURKB - MAD2L

Marima et al. [27] show that overexpression of AURKB augments the expression of MAD2L2 and both work synergistically in tumorigenesis and DNA damage response. In colorectal cancer cells treated with ETC-1922159, MAD2L family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these MAD2L member along with AURKB.
Table 15 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 16 generated from analysis of the ranks in Table 15. The Table 15 shows rankings of individual members w.r.t AURKB. MAD2L1 - AURKB shows low ranking of 114 (laplace), 109 (linear) and 477 (rbf). MAD2L2 - AURKB shows low ranking of 852 (laplace) and 678 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
One can also interpret the results of the Table 15 graphically, with the following influences - • MAD2L family w.r.t AURKB with AURKB − > MAD2L-1/2.

2.1.9. AURKB - HOX

Kim et al. [28] observe that castration-resistant prostate cancer deploy the bromodomain and BRD4 to epigenetically regulate HOXB13 gene expression which activates AURKA/AURKB. In colorectal cancer cells treated with ETC-1922159, HOX family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these HOX member along with AURKB.
Table 17 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 18 generated from analysis of the ranks in Table 17. The Table 17 shows rankings of individual members w.r.t AURKB. HOXB9 - AURKB shows low ranking of 447 (laplace), 1286 (linear) and 1240 (rbf). HOXB8 - AURKB shows low ranking of 689 (laplace), 236 (linear) and 128 (rbf). HOXB5 - AURKB shows low ranking of 1297 (laplace), 1415 (linear) and 1006 (rbf). HOXA9 - AURKB shows low ranking of 1430 (linear) and 1415 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, HOXB4, HOXA11, HOXB13, HOXB3 and HOXB7 showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 17 graphically, with the following influences - • HOX family w.r.t AURKB with AURKB − > HOX-B9/B8/B5/A9.

2.1.10. AURKB - DHX

Zhu et al. [29] show that AURKB targets DHX9 to promote hepatocellular carcinoma progression. In colorectal cancer cells treated with ETC-1922159, DHX family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these DHX member along with AURKB.
Table 19 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 20 generated from analysis of the ranks in Table 19. The Table 19 shows rankings of individual members w.r.t AURKB. DHX33 - AURKB shows low ranking of 606 (laplace), 947 (linear) and 1374 (rbf). DHX57 - AURKB shows low ranking of 1113 (laplace), 754 (linear) and 642 (rbf). DHX37 - AURKB shows low ranking of 1432 (linear) and 1430 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, DHX40, DHX35, DHX30 and DHX9 showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 19 graphically, with the following influences - • DHX family w.r.t AURKB with AURKB − > DHX-33/57/37.

2.1.11. AURKB - PLK

Chu et al. [30] show that AURKB activation requires Survivin priming phosphorylation, which is catalyzed by PLK1. Inhibition of PLK1 prevents AURKB activation and correct spindle microtubule attachment. In colorectal cancer cells treated with ETC-1922159, PLK family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these PLK member along with AURKB.
Table 21 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 22 generated from analysis of the ranks in Table 21. The Table 21 shows rankings of individual members w.r.t AURKB. PLK1 - AURKB shows low ranking of 732 (laplace), 755 (linear) and 522 (rbf). PLK4 - AURKB shows low ranking of 958 (laplace), 454 (linear) and 37 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
One can also interpret the results of the Table 21 graphically, with the following influences - • PLK family w.r.t AURKB with AURKB − > PLK-1/4.

2.1.12. AURKB - BUB

Roy et al. [31] show evidence that AURKB phosphorylates BUB1 which maintains spindle assembly checkpoint signaling. In colorectal cancer cells treated with ETC-1922159, BUB family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these BUB member along with AURKB.
Table 23 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 24 generated from analysis of the ranks in Table 23. The Table 23 shows rankings of individual members w.r.t AURKB. BUB1 - AURKB shows low ranking of 58 (laplace), 239 (linear) and 476 (rbf). BUB1B - AURKB shows low ranking of 100 (laplace), 103 (linear) and 537 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, BUB3 showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 23 graphically, with the following influences - • BUB family w.r.t AURKB with AURKB − > BUB-1/1B.

2.1.13. AURKB - TOP

Via proteomic analysis Morrison et al. [32] identified phosphorylated TOP2A as a potential AURKB substrate. In colorectal cancer cells treated with ETC-1922159, TOP family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these TOP member along with AURKB.
Table 25 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 26 generated from analysis of the ranks in Table 25. The Table 25 shows rankings of individual members w.r.t AURKB. TOP2A - AURKB shows low ranking of 23 (laplace), 19 (linear) and 36 (rbf). TOP1MT - AURKB shows low ranking of 563 (laplace), 618 (linear) and 418 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, TOPBP1 and TOP2B showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 25 graphically, with the following influences - • TOP family w.r.t AURKB with AURKB − > TOP-2A/1MT.

2.1.14. AURKB - CDK

Lee et al. [33] demonstrate that CDK4 could occupy the promoter region of genes like AURKB and CENPP. Further, gain- and loss- of function experiments showed that CDK4 regulated expressiong of AURKB and CENPP. In colorectal cancer cells treated with ETC-1922159, CDK family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these CDK member along with AURKB.
Table 27 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 28 generated from analysis of the ranks in Table 27. The Table 27 shows rankings of individual members w.r.t AURKB. CDK1 - AURKB shows low ranking of 30 (laplace), 4 (linear) and 206 (rbf). CDK20 - AURKB shows low ranking of 653 (laplace), 832 (linear) and 1002 (rbf). CDK4 - AURKB shows low ranking of 1453 (laplace) and 1338 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, CDK6 showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 27 graphically, with the following influences - • CDK family w.r.t AURKB with AURKB − > CDK-1/20/4.

2.1.15. AURKB - ALKBH

Zhang et al. [34] suggest that ALKBH5 may proliferate renal cell carcinoma by stabilizing AURKB. In colorectal cancer cells treated with ETC-1922159, ALKBH family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these ALKBH member along with AURKB.
Table 29 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 30 generated from analysis of the ranks in Table 29. The Table 29 shows rankings of individual members w.r.t AURKB. ALKBH2 - AURKB shows low ranking of 494 (laplace), 758 (linear) and 438 (rbf). ALKBH8 - AURKB shows low ranking of 1013 (laplace), 942 (linear) and 632 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, ALKBH4 showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 29 graphically, with the following influences - • ALKBH family w.r.t AURKB with AURKB − > ALKBH-2/8.

2.1.16. AURKB - PRMT

Kim et al. [35] show that asymmetric dimethylation on histone H3 by PRMT6 recruits the chromosomal passenger complex to chromosome arms and facilitates histone H3S10 phosphorylation by AURKB. In colorectal cancer cells treated with ETC-1922159, PRMT family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these PRMT member along with AURKB.
Table 31 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 32 generated from analysis of the ranks in Table 31. The Table 31 shows rankings of individual members w.r.t AURKB. PRMT6 - AURKB shows low ranking of 769 (laplace), 418 (linear) and 626 (rbf). PRMT1 - AURKB shows low ranking of 1388 (laplace) and 686 (linear). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
One can also interpret the results of the Table 31 graphically, with the following influences - • PRMT family w.r.t AURKB with AURKB − > PRMT-6/1.

2.1.17. AURKB - SGO

Asai et al. [36] show that SET is recruited through interaction with SGO2 (also known as SGOL2), and maintains AURKB activity by counteracting PP2A in mitotic cells, at the inner centromere. In colorectal cancer cells treated with ETC-1922159, SGO family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these SGO member along with AURKB.
Table 33 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 34 generated from analysis of the ranks in Table 33. The Table 33 shows rankings of individual members w.r.t AURKB. SGOL1 - AURKB shows low ranking of 225 (laplace), 146 (linear) and 122 (rbf). SGOL2 - AURKB shows low ranking of 534 (laplace), 473 (linear) and 284 (rbf). SGOL1-AS1 - AURKB shows low ranking of 239 (laplace), 174 (linear) and 100 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
One can also interpret the results of the Table 33 graphically, with the following influences - • SGO family w.r.t AURKB with AURKB − > SGO-L1/L2/L1-AS1.

2.1.18. AURKB - SKA

The spindle and kinetochore-associated (SKA) complex is required for chromosome segregation and consists of two copies each of SKA1, SKA2, and SKA3 proteins. SKA complex regulates, and is regulated by AURKB as shown by Redli et al. [37]. Also, Chan et al. [38] show that AURKB phosphorylates both SKA1 and SKA3 to inhibit the kinetochore localization of the SKA complex. Finally, Zhang et al. [39] show that CDK1 phosphorylates SKA3 which occurs during mitosis and is required for the kinetochore localization of the SKA complex. In colorectal cancer cells treated with ETC-1922159, SKA family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these SKA member along with AURKB.
Table 35 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 36 generated from analysis of the ranks in Table 35. The Table 35 shows rankings of individual members w.r.t AURKB. SKA1 - AURKB shows low ranking of 56 (laplace), 75 (linear) and 324 (rbf). SKA3 - AURKB shows low ranking of 128 (laplace), 140 (linear) and 160 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, SKA2 showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 35 graphically, with the following influences - • SKA family w.r.t AURKB with AURKB − > SKA-1/3.

2.1.19. AURKB - GAS

Fackler et al. [40] show that GAS2L3 associates with AURKB and survivin. In colorectal cancer cells treated with ETC-1922159, GAS family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these GAS member along with AURKB.
Table 37 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 38 generated from analysis of the ranks in Table 37. The Table 37 shows rankings of individual members w.r.t AURKB. GAS5 - AURKB shows low ranking of 1100 (laplace) and 1482 (rbf). GAS2L3 - AURKB shows low ranking of 1577 (laplace) and 1329 (rbf). GAS6 - AURKB shows low ranking of 1362 (linear) and 1122 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
One can also interpret the results of the Table 37 graphically, with the following influences - • GAS family w.r.t AURKB with AURKB − > GAS-5/2L3/6.

2.1.20. AURKB - KIF

Via experiments and mathematical modeling, Uehara et al. [41] demonstrate that AURKB activity gradient determines the spatial distribution of KIF2A and limits KIF2A mediated depolymerization in an interchromosomal microtubule length dependent fashion. In colorectal cancer cells treated with ETC-1922159, KIF family members and AURKB, were found to be down regulated and their regulation was recorded independently. I was able to rank 2nd order combination of these KIF member along with AURKB.
Table 39 shows rankings of these combinations. Followed by this is the unexplored combinatorial hypotheses in Table 40 generated from analysis of the ranks in Table 39. The Table 39 shows rankings of individual members w.r.t AURKB. KIF4A - AURKB shows low ranking of 24 (laplace), 13 (linear) and 21 (rbf). KIF11 - AURKB shows low ranking of 40 (laplace), 29 (linear) and 139 (rbf). KIF2C - AURKB shows low ranking of 42 (laplace), 67 (linear) and 41 (rbf). KIF20A - AURKB shows low ranking of 61 (laplace), 40 (linear) and 445 (rbf). KIF23 - AURKB shows low ranking of 70 (laplace), 69 (linear) and 281 (rbf). KIF15 - AURKB shows low ranking of 92 (laplace), 57 (linear) and 94 (rbf). KIF14 - AURKB shows low ranking of 110 (laplace), 190 (linear) and 161 (rbf). KIFC1 - AURKB shows low ranking of 139 (laplace), 452 (linear) and 367 (rbf). KIF20B - AURKB shows low ranking of 155 (laplace), 253 (linear) and 896 (rbf). KIF22 - AURKB shows low ranking of 184 (laplace), 192 (linear) and 300 (rbf). KIF18A - AURKB shows low ranking of 213 (laplace), 129 (linear) and 649 (rbf). KIF18B - AURKB shows low ranking of 229 (laplace), 249 (linear) and 19 (rbf). KIF9 - AURKB shows low ranking of 1167 (laplace), 776 (linear) and 1111 (rbf). KIF7 - AURKB shows low ranking of 1380 (laplace), 697 (linear) and 1147 (rbf). These rankings point to the synergy existing between the two components, which have been down regulated after the drug treatment.
Further, KIF27 and KIF13A showed high ranking with AURKB, thus indicating that they might not be working synergistically with AURKB, before the drug treatment.
One can also interpret the results of the Table 39 graphically, with the following influences - • KIF family w.r.t AURKB with AURKB − > KIF-4A / 11 / 2C / 20A / 23 / 15 / 14 / C1 / 20B / 22 / 18A / 18B / 9 / 7.

3. Conclusion

Presented here are a range of multiple synergistic AURKB 2nd order combinations that were ranked via a machine learning based search engine. Via majority voting across the ranking methods, it was possible to find plausible unexplored synergistic combinations of AURKB-X that might be prevalent in CRC cells after treatment with ETC-1922159 drug.

Author Contributions

Concept, design, in silico implementation - SS. Analysis and interpretation of results - SS. Manuscript writing - SS. Manuscript revision - SS. Approval of manuscript - SS

Source of Data

Data used in this research work was released in a publication in Madan et al. [42].

Acknowledgments

Special thanks to Mrs. Rita Sinha and Mr. Prabhat Sinha for supporting the author financially, without which this work could not have been made possible.

Conflicts of Interest

There are no conflicts to declare.

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Table 1. 2nd order interaction ranking between AURKB VS INDIVIDUAL family members.
Table 1. 2nd order interaction ranking between AURKB VS INDIVIDUAL family members.
Ranking INDIVIDUAL family VS AURKB
Ranking of INDIVIDUAL family w.r.t AURKB
laplace linear rbf
ZWINT - AURKB 1 38 18
INCENP - AURKB 678 941 571
TPX2 - AURKB 10 10 7
WNT10B - AURKB 583 491 578
CDT1 - AURKB 318 135 290
GTSE1 - AURKB 537 283 137
VRK1 - AURKB 181 848 229
RECQL4 - AURKB 897 439 508
GSG2 - AURKB 74 189 375
Table 2. 2nd order combinatorial hypotheses between AURKB and Individual members.
Table 2. 2nd order combinatorial hypotheses between AURKB and Individual members.
Unexplored combinatorial hypotheses
Individual members w.r.t AURKB
ZWINT / INCENP / TPX2 / WNT10B AURKB
CDT1 / GTSE1 / VRK1 / RECQL4 / GSG2 AURKB
Table 3. 2nd order interaction ranking between AURKB VS CENP family.
Table 3. 2nd order interaction ranking between AURKB VS CENP family.
Ranking CENP family VS AURKB
Ranking of CENP family w.r.t AURKB
laplace linear rbf
CENPU - AURKB 38 35 11
CENPF - AURKB 39 58 136
CENPH - AURKB 83 22 88
CENPA - AURKB 122 49 38
CENPE - AURKB 143 27 829
CENPJ - AURKB 164 113 592
CENPW - AURKB 217 241 512
CENPK - AURKB 232 276 49
CENPI - AURKB 368 521 65
CENPN - AURKB 546 906 366
CENPM - AURKB 713 414 858
CENPL - AURKB 748 1117 695
CENPO - AURKB 1962 2075 2344
CENPV - AURKB 2609 2669 2611
Table 4. 2nd order combinatorial hypotheses between AURKB and CENP family.
Table 4. 2nd order combinatorial hypotheses between AURKB and CENP family.
Unexplored combinatorial hypotheses
CENP family w.r.t AURKB
CENP-U/F/H/A/E/J/W/K/I/N/M/L AURKB
Table 5. 2nd order interaction ranking between AURKB VS E2F family.
Table 5. 2nd order interaction ranking between AURKB VS E2F family.
Ranking E2F family VS AURKB
Ranking of E2F family w.r.t AURKB
laplace linear rbf
E2F8 - AURKB 95 252 125
E2F1 - AURKB 499 243 1086
E2F7 - AURKB 1034 777 313
E2F2 - AURKB 1057 1498 839
E2F5 - AURKB 2615 1462 2727
Table 6. 2nd order combinatorial hypotheses between AURKB and E2F family.
Table 6. 2nd order combinatorial hypotheses between AURKB and E2F family.
Unexplored combinatorial hypotheses
E2F family w.r.t AURKB
E2F-8/1/7/2 AURKB
Table 7. 2nd order interaction ranking between AURKB VS CDC family.
Table 7. 2nd order interaction ranking between AURKB VS CDC family.
Ranking CDC family VS AURKB
Ranking of CDC family w.r.t AURKB
laplace linear rbf
CDC20 - AURKB 60 48 260
CDC7 - AURKB 116 52 20
CDC45 - AURKB 157 50 111
CDC25C - AURKB 235 153 282
CDC25A - AURKB 340 364 798
CDC6 - AURKB 1080 708 1075
CDC23 - AURKB 1852 1250 2441
CDC123 - AURKB 2437 1646 2207
Table 8. 2nd order combinatorial hypotheses between AURKB and CDC family.
Table 8. 2nd order combinatorial hypotheses between AURKB and CDC family.
Unexplored combinatorial hypotheses
CDC family w.r.t AURKB
CDC-20/7/45/25C/25A/6 AURKB
Table 9. 2nd order interaction ranking between AURKB VS USP family.
Table 9. 2nd order interaction ranking between AURKB VS USP family.
Ranking USP family VS AURKB
Ranking of USP family w.r.t AURKB
laplace linear rbf
USP13 - AURKB 129 240 862
USP10 - AURKB 1038 1852 2502
USP28 - AURKB 1082 798 935
USP1 - AURKB 2170 2306 1900
USP36 - AURKB 2647 1986 1449
USP39 - AURKB 2729 2633 2242
Table 10. 2nd order combinatorial hypotheses between AURKB and USP family.
Table 10. 2nd order combinatorial hypotheses between AURKB and USP family.
Unexplored combinatorial hypotheses
USP family w.r.t AURKB
USP-13/28 AURKB
Table 11. 2nd order interaction ranking between AURKB VS NUP family.
Table 11. 2nd order interaction ranking between AURKB VS NUP family.
Ranking RANBP/NUP family VS AURKB
Ranking of RANBP/NUP family w.r.t AURKB
laplace linear rbf
RANBP1 - AURKB 448 1179 638
RANBP17 - AURKB 2185 2291 925
NUP35 - AURKB 761 421 34
NUP155 - AURKB 886 1471 1554
NUP210 - AURKB 937 520 1725
NUP43 - AURKB 1033 405 959
NUP37 - AURKB 1160 863 1346
NUP160 - AURKB 1181 742 1412
NUP107 - AURKB 1194 1527 883
NUP93 - AURKB 1319 1943 1959
NUP133 - AURKB 2195 2049 1324
NUP85 - AURKB 2272 2534 2674
NUP88 - AURKB 2343 2449 1742
NUP205 - AURKB 2456 1676 2234
NUP54 - AURKB 2586 2617 2735
NUP188 - AURKB 2652 1224 2442
NUP62 - AURKB 2682 2742 2712
Table 12. 2nd order combinatorial hypotheses between AURKB and NUP family.
Table 12. 2nd order combinatorial hypotheses between AURKB and NUP family.
Unexplored combinatorial hypotheses
NUP family w.r.t AURKB
RANBP1 AURKB
NUP-35/155/210/43/37/160/107 AURKB
Table 13. 2nd order interaction ranking between AURKB VS GEMIN family.
Table 13. 2nd order interaction ranking between AURKB VS GEMIN family.
Ranking GEMIN family VS AURKB
Ranking of GEMIN family w.r.t AURKB
laplace linear rbf
GEMIN6 - AURKB 367 971 523
GEMIN5 - AURKB 595 841 345
GEMIN2 - AURKB 954 687 2150
GEMIN4 - AURKB 1556 659 2082
GEMIN7 - AURKB 2447 1968 2434
Table 14. 2nd order combinatorial hypotheses between AURKB and GEMIN family.
Table 14. 2nd order combinatorial hypotheses between AURKB and GEMIN family.
Unexplored combinatorial hypotheses
GEMIN family w.r.t AURKB
GEMIN-6/5/2 AURKB
Table 15. 2nd order interaction ranking between AURKB VS MAD2L family.
Table 15. 2nd order interaction ranking between AURKB VS MAD2L family.
Ranking MAD2L family VS AURKB
Ranking of MAD2L family w.r.t AURKB
laplace linear rbf
MAD2L1 - AURKB 114 109 477
MAD2L2 - AURKB 852 1872 678
Table 16. 2nd order combinatorial hypotheses between AURKB and MAD2L family.
Table 16. 2nd order combinatorial hypotheses between AURKB and MAD2L family.
Unexplored combinatorial hypotheses
MAD2L family w.r.t AURKB
MAD2L-1/2 AURKB
Table 17. 2nd order interaction ranking between AURKB VS HOX family.
Table 17. 2nd order interaction ranking between AURKB VS HOX family.
Ranking HOX family VS AURKB
Ranking of HOX family w.r.t AURKB
laplace linear rbf
HOXB9 - AURKB 447 1286 1240
HOXB8 - AURKB 689 236 128
HOXB4 - AURKB 1101 1939 1711
HOXB5 - AURKB 1297 1415 1006
HOXA11 - AURKB 1505 2329 1721
HOXB13 - AURKB 2314 2670 2228
HOXB3 - AURKB 2380 2593 2026
HOXB7 - AURKB 2435 2518 2668
HOXA9 - AURKB 2643 1430 1415
Table 18. 2nd order combinatorial hypotheses between AURKB and HOX family.
Table 18. 2nd order combinatorial hypotheses between AURKB and HOX family.
Unexplored combinatorial hypotheses
HOX family w.r.t AURKB
HOX-B9/B8/B5/A9 AURKB
Table 19. 2nd order interaction ranking between AURKB VS DHX family.
Table 19. 2nd order interaction ranking between AURKB VS DHX family.
Ranking DHX family VS AURKB
Ranking of DHX family w.r.t AURKB
laplace linear rbf
DHX33 - AURKB 606 947 1374
DHX57 - AURKB 1113 754 642
DHX40 - AURKB 1316 1679 1595
DHX35 - AURKB 1448 2012 2312
DHX30 - AURKB 1658 2235 2205
DHX37 - AURKB 1715 1432 1430
DHX9 - AURKB 2560 2434 2065
Table 20. 2nd order combinatorial hypotheses between AURKB and DHX family.
Table 20. 2nd order combinatorial hypotheses between AURKB and DHX family.
Unexplored combinatorial hypotheses
DHX family w.r.t AURKB
DHX-33/57/37 AURKB
Table 21. 2nd order interaction ranking between AURKB VS PLK family.
Table 21. 2nd order interaction ranking between AURKB VS PLK family.
Ranking PLK family VS AURKB
Ranking of PLK family w.r.t AURKB
laplace linear rbf
PLK1 - AURKB 732 755 522
PLK4 - AURKB 958 454 37
Table 22. 2nd order combinatorial hypotheses between AURKB and PLK family.
Table 22. 2nd order combinatorial hypotheses between AURKB and PLK family.
Unexplored combinatorial hypotheses
PLK family w.r.t AURKB
PLK-1/4 AURKB
Table 23. 2nd order interaction ranking between AURKB VS BUB family.
Table 23. 2nd order interaction ranking between AURKB VS BUB family.
Ranking BUB family VS AURKB
Ranking of BUB family w.r.t AURKB
laplace linear rbf
BUB1 - AURKB 58 239 476
BUB1B - AURKB 100 103 537
BUB3 - AURKB 1773 1836 747
Table 24. 2nd order combinatorial hypotheses between AURKB and BUB family.
Table 24. 2nd order combinatorial hypotheses between AURKB and BUB family.
Unexplored combinatorial hypotheses
BUB family w.r.t AURKB
BUB-1/1B AURKB
Table 25. 2nd order interaction ranking between AURKB VS TOP family.
Table 25. 2nd order interaction ranking between AURKB VS TOP family.
Ranking TOP family VS AURKB
Ranking of TOP family w.r.t AURKB
laplace linear rbf
TOP2A - AURKB 23 19 36
TOP1MT - AURKB 563 618 418
TOPBP1 - AURKB 1950 1973 2279
TOP2B - AURKB 2322 1739 2033
Table 26. 2nd order combinatorial hypotheses between AURKB and TOP family.
Table 26. 2nd order combinatorial hypotheses between AURKB and TOP family.
Unexplored combinatorial hypotheses
TOP family w.r.t AURKB
TOP-2A/1MT AURKB
Table 27. 2nd order interaction ranking between AURKB VS CDK family.
Table 27. 2nd order interaction ranking between AURKB VS CDK family.
Ranking CDK family VS AURKB
Ranking of CDK family w.r.t AURKB
laplace linear rbf
CDK1 - AURKB 30 4 206
CDK20 - AURKB 653 832 1002
CDK4 - AURKB 1453 2213 1338
CDK6 - AURKB 2263 2388 2424
Table 28. 2nd order combinatorial hypotheses between AURKB and CDK family.
Table 28. 2nd order combinatorial hypotheses between AURKB and CDK family.
Unexplored combinatorial hypotheses
CDK family w.r.t AURKB
CDK-1/20/4 AURKB
Table 29. 2nd order interaction ranking between AURKB VS ALKBH family.
Table 29. 2nd order interaction ranking between AURKB VS ALKBH family.
Ranking ALKBH family VS AURKB
Ranking of ALKBH family w.r.t AURKB
laplace linear rbf
ALKBH2 - AURKB 494 758 438
ALKBH8 - AURKB 1013 942 632
ALKBH4 - AURKB 1599 2324 2640
Table 30. 2nd order combinatorial hypotheses between AURKB and ALKBH family.
Table 30. 2nd order combinatorial hypotheses between AURKB and ALKBH family.
Unexplored combinatorial hypotheses
ALKBH family w.r.t AURKB
ALKBH-2/8 AURKB
Table 31. 2nd order interaction ranking between AURKB VS PRMT family.
Table 31. 2nd order interaction ranking between AURKB VS PRMT family.
Ranking PRMT family VS AURKB
Ranking of PRMT family w.r.t AURKB
laplace linear rbf
PRMT6 - AURKB 769 418 626
PRMT1 - AURKB 1388 686 1818
Table 32. 2nd order combinatorial hypotheses between AURKB and PRMT family.
Table 32. 2nd order combinatorial hypotheses between AURKB and PRMT family.
Unexplored combinatorial hypotheses
PRMT family w.r.t AURKB
PRMT-6/1 AURKB
Table 33. 2nd order interaction ranking between AURKB VS SGO family.
Table 33. 2nd order interaction ranking between AURKB VS SGO family.
Ranking SGO family VS AURKB
Ranking of SGO family w.r.t AURKB
laplace linear rbf
SGOL1 - AURKB 225 146 122
SGOL2 - AURKB 534 473 284
SGOL1-AS1 - AURKB 239 174 100
Table 34. 2nd order combinatorial hypotheses between AURKB and SGO family.
Table 34. 2nd order combinatorial hypotheses between AURKB and SGO family.
Unexplored combinatorial hypotheses
SGO family w.r.t AURKB
SGO-L1/L2/L1-AS1 AURKB
Table 35. 2nd order interaction ranking between AURKB VS SKA family.
Table 35. 2nd order interaction ranking between AURKB VS SKA family.
Ranking SKA family VS AURKB
Ranking of SKA family w.r.t AURKB
laplace linear rbf
SKA1 - AURKB 56 75 324
SKA2 - AURKB 1328 2317 2609
SKA3 - AURKB 128 140 160
Table 36. 2nd order combinatorial hypotheses between AURKB and SKA family.
Table 36. 2nd order combinatorial hypotheses between AURKB and SKA family.
Unexplored combinatorial hypotheses
SKA family w.r.t AURKB
SKA-1/3 AURKB
Table 37. 2nd order interaction ranking between AURKB VS GAS family.
Table 37. 2nd order interaction ranking between AURKB VS GAS family.
Ranking GAS family VS AURKB
Ranking of GAS family w.r.t AURKB
laplace linear rbf
GAS5 - AURKB 1100 1772 1482
GAS2L3 - AURKB 1577 1871 1329
GAS6 - AURKB 1637 1362 1122
Table 38. 2nd order combinatorial hypotheses between AURKB and GAS family.
Table 38. 2nd order combinatorial hypotheses between AURKB and GAS family.
Unexplored combinatorial hypotheses
GAS family w.r.t AURKB
GAS-5/2L3/6 AURKB
Table 39. 2nd order interaction ranking between AURKB VS KIF family.
Table 39. 2nd order interaction ranking between AURKB VS KIF family.
Ranking KIF family VS AURKB
Ranking of KIF family w.r.t AURKB
laplace linear rbf laplace linear rbf
KIF4A - AURKB 24 13 21 KIF11 - AURKB 40 29 139
KIF2C - AURKB 42 67 41 KIF20A - AURKB 61 40 445
KIF23 - AURKB 70 69 281 KIF15 - AURKB 92 57 94
KIF14 - AURKB 110 190 161 KIFC1 - AURKB 139 452 367
KIF20B - AURKB 155 253 896 KIF22 - AURKB 184 192 300
KIF18A - AURKB 213 129 649 KIF18B - AURKB 229 249 19
KIF9 - AURKB 1167 776 1111 KIF7 - AURKB 1380 697 1147
KIF27 - AURKB 1581 1833 1081 KIF13A - AURKB 2740 1774 2350
Table 40. 2nd order combinatorial hypotheses between AURKB and KIF family.
Table 40. 2nd order combinatorial hypotheses between AURKB and KIF family.
Unexplored combinatorial hypotheses
KIF family w.r.t AURKB
KIF-4A/11/2C/20A/23/15/14/C1/20B/22/18A/18B/9/7 AURKB
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