KIAA1735/Dixin DIX domain con aining 1 (DIXDC1) :
Time beha iou al s udy o 3 d o de combina ions in
WNT3A s imula ed HEK 293 cells
sh ip akash sinha
Independen Resea che ; O cid ID : o cid.o g/0000-0001-7027-5788
Add ess : 104-Madhu isha Heigh s Phase 1, Risali, Bhilai-490006, India
Co esponding au ho email : sinha.sh ip [email protected]
Abs ac
DIXDC1, when ac i e, is known o s op cance me as asis due o ex eme s ickiness,
bo h in i o and in i o and i u ns ou o be inhibi ed in cance and mes as asis. Gu-
j al and MacBea h [1] p o ides a quan i a i e, and dynamic s udy o WNT3A-media ed
s imula ion o HEK 293 cells, whe e hey eco d ime based exp ession p o iles o se -
e al esponse genes which co ela ed signi ican ly wi h p oli e a ion and mig a ion. By
moni o ing he dynamics o gene exp ession using sel -o ganizing maps, hey iden i ied
clus e s o genes ha exhibi simila exp ession dynamics and unco e ed p e iously
un ecognized posi i e and nega i e eedback loops. Howe e , hei s udy depic s/uses
singula measu emen s o indi idual gene exp ession a di e en ime snapsho s/poin s
o in e he sys em wide analysis o he pa hway. A any pa icula ime poin , i is o -
en he case ha genes a e wo king syne gis ically in combina ions, e en hough hei
exp ession measu emen s a e singula in na u e. He e, I •enume a e and ank all 2415
DIXDC1 ela ed 3 d o de combina ions in a o es o 71C3combina ions using ou
di e en sensi i i y me hods; •show he conse ed ankings o DIXDC1-X-X combi-
na ions, which poin o exis ence o biological syne gy o some o hese combina ions
ac oss he di e en sensi i i y me hods; and •s udy he beha iou o some o hese
combina ions ela ed o WNT3A esponse genes ha a e anked by he machine lea n-
ing sea ch engine (Sinha [2]) in ime. Pa e ns o combina ions eme ge, some o which
ha e been es ed in we lab, while o he s equi e u he we lab analysis.
Keywo ds: Sensi i i y analysis, Suppo ec o anking, Hilbe Schmid
Independence C i e ion indices (HSIC) and Sobol indicies, WNT3A
ITime beha iou al s udy o 3-od DIXDC1 comb. in WNT3A s imula ed cells
1Aspec s o unpublished wo k we e p esen ed in a pos e session a Cell Symposia: Technology. Biology.
Da a Science, 9-11 Oc obe 2016, Be keley, Cali o nia, USA.
P ep in submi ed o P ep in Ma ch 5, 2025
1. Signi icance
Sinha [2] ecen ly demons a ed he use o machine lea ning based sea ch engine o
ank/ e eal gene combina ions a 2nd o de o he ime se ies da a by Guj al and
MacBea h [1] and showed how i is possible o loca e combina ions o p io i y ha
migh be wo king syne gis ically, using sensi i i y me hods and powe ul suppo ec-
o anking algo i hm. Howe e , he p oblem explodes combina o ially wi h e en a
small se o 71 eco ded genes in he s udy by Guj al and MacBea h [1], when one
s eps o explo e 3 d o de combina ions. Wi h he o al numbe o 71C3(= 57155)
combina ions, i becomes nea ly impossible o any biologis o s udy he sys em wide
dynamics o any pa hway. Also, he amoun o ime usually needed o sea ch o and
es a combina ion is a mo e han he sea ch down by he machine lea ning based
sea ch engine. He e, I ex end he esea ch wo k by Sinha [2] o conduc a beha io al
s udy o 3 d o de DIXDC1 ela ed combina ions using indi idual gene exp essions
measu ed in ime, in WNT3A s imula ed HEK 293 cells.
2. In oduc ion
The de ails o he machine lea ning based sea ch engine has been ecen ly published in
Sinha [2] and deployed o explo e he 2nd o de combina ions o genes in he da a se
p o ided by Guj al and MacBea h [1]. Ne e heless, he e, I poin o he undamen als
o he published wo k o comple eness.
2.1. A combina o ial p oblem
Sensi i i y analysis plays a majo ole in compu ing he s eng h o he in luence o
in ol ed ac o s in any phenomena unde in es iga ion. When applied o exp ession
p o iles o a ious in a/ex acellula ac o s ha o m an in eg al pa o a signaling
pa hway, he a iance and densi y based analysis yields a ange o sensi i i y indices
o indi idual as well as a ious combina ions o ac o s. These combina ions deno e
he highe o de in e ac ions among he in ol ed ac o s. Compu a ion o highe o -
de in e ac ions is o en ime consuming bu i gi es a chance o explo e he a ious
combina ions ha migh be o in e es in he wo king mechanism o he pa hway. Fo
example, in a ange o ou h o de combina ions among he a ious ac o s o he Wn
pa hway, i would be easy o assess he in luence o he des uc ion complex o med by
APC, AXIN, CSKI and GSK3 in e ac ion. Bu he e ec o hese combina ions a y
o e ime as measu emen s o old changes and de ia ions in old changes a y. So
i is impe a i e o know how an in e ac ion o a combina ion o he in ol ed ac o s
beha e in ime and Sinha [2] de elops a p ocedu e o ack he beha iou by exploi ing
he in luences o hese in ol ed ac o s.
2.2. A possible solu ion
In his wo k, a e es ima ing he indi idual e ec s o ac o s o a highe o de combi-
na ion, he indi idual indices a e conside ed as disc imina i e ea u es. A combina ion,
2
hen, is a ea u e se in highe o de (≥2 ,i.e mul i a ia e). Wi h an excessi ely la ge
numbe o ac o s in ol ed in he pa hway, i is di icul o sea ch o impo an com-
bina ions in a wide sea ch space o e di e en o de s. Exploi ing he analogy wi h
he issues o p io i izing webpages using anking algo i hms, o a pa icula o de , a
ull se o combina ions o in e ac ions can hen be p io i ized based on hese ea u es
using a powe ul anking algo i hm ia suppo ec o s Joachims [3]. Reco ding he
changing ankings o he combina ions o e ime e eals how highe o de in e ac ions
beha e wi hin he pa hway and when an in e en ion migh be necessa y o in luence
he in e ac ion wi hin he pa hway.
2.3. KIAA1735/Dixin DIX domain con aining 1 (DIXDC1)
Dishe elled DVL-1/2/3 a e DIX-domain p o eins implica ed in he WNT signaling
pa hway. Ka oh and Ka oh [4] sea ched ound an uncha ac e ized human KIAA1735
gene encoding a no el DIX-domain p o ein, using bioin o ma ics. They iden i ied
mouse o holog o human KIAA1735 gene, and he nucleo ide sequence o mouse
KIAA1735 cDNA was de e mined in silico by assembling nucleo ide sequences o
ESTs BY753211, BQ931084, CA750490, BQ960056 and a 5’- unca ed pa ial cDNA
AK082960. Myosine- ail homologous (MTH) domain and C- e minal DIX domain
we e conse ed be ween human KIAA1735 and mouse KIAA1735 p o eins. A y o-
sine phospho yla ion si e (Ty 242) wi hin he MTH domain was conse ed be ween
human KIAA1735 and mouse KIAA1735 p o eins. KIAA1735 gene (consis ing o
16 exons), was abou 45 kb in size and on human ch omosome 11q23.1, was loca ed
be ween D11S1391 and D11S1347 loci, he egion dele ed in spo adic b eas cance .
This was he i s epo on comp ehensi e cha ac e iza ion o he KIAA1735 gene.
To become mobile, cance cells usually o e ide cellula machine y ha keeps cells
oo ed wi hin hei espec i e loca ions. De iously, cance can swi ch on and o molec-
ula ancho s p o uding om he cell memb ane (called ocal adhesion complexes),
p epa ing he cell o mig a ion. This allows cance cells o begin he p ocesses o
a e se he body h ough he bloods eam and ake up esidence in new o gans. Can-
ce s missing pola iza ion- ela ed p o ein LKB1 o se ine/ h eonine kinase 11 (Peu z-
Jeghe s synd ome) (LKB1/STK11) a e o en agg essi e, apidly sp eading h ough
he body. Howe e , i was no known, how LKB1 and ocal adhesions we e con-
nec ed. In an medical p ess elease by he Salk Ins i u e on July 17, 2014 in h ps://
medicalxp ess.com/news/2014-07-gene-deadly-cance .h ml#nRl , he Salk
Ins i u e eam ound he connec ion and a new a ge o he apy: DIXDC1. They dis-
co e ed ha DIXDC1 ecei ed ins uc ions om LKB1 o go o ocal adhesions and
change hei size and numbe . When DIXDC1 was ac i e, ocal adhesions g ew la ge
and s icky, ancho ing cells o hei spo , while when DIXDC1 was inac i e, ocal ad-
hesions became small and nume ous, esul ing in hund eds o small hands ha pull he
cell o wa d in esponse o ex acellula cues. Tha inc eased endency o be mobile,
aids in he escape om, o example, he lungs and allows umo cells o su i e a el
h ough he bloods eam and dock a o gans h oughou he body. I u ned ou ha
DIXDC1 was inhibi ed in cance and me as asis.
I p esen 3 d o de combina ions o DIXDC1 wi h o he genes, ha he machine
lea ning based sea ch engine poin s o, as possible syne gis ic combina ions ha migh
3
be wo king in ime.
3. Me hods
Please e e o sec ions o Sinha [2] o me hods, design o s udy and analysis o da a
o 2nd o de combina ions. The same me hod and design o s udy is used o gene a e
esul s o 3 d o de combina ions p esen ed in his s udy.
4. Time se ies da a
Guj al and MacBea h [1] p esen a se o 71 WNT- ela ed gene exp ession alues o 6
di e en imes poin s o e a ange o 24-hou pe iod using qPCR. The changes ep e-
sen he old-change in he exp ession le els o genes in 200 ng/mL WNT3A-s imula ed
HEK 293 cells in ime ela i e o hei le els in uns imula ed, se um-s a ed cells a 0-
hou . Guj al and MacBea h [1] s a e ha qPCR da a a e he means o h ee biological
eplica es. Only genes whose mean ansc ip le els changed by mo e han wo- old a
one o mo e ime poin s du ing he 24-hou ime cou se we e conside ed signi ican .
Posi i e (nega i e) numbe s ep esen up (down) - egula ion. We ha e al eady co e ed
he issues ela ed o hese da a se s in de ail in Sinha [5]. Reade s a e eques ed o go
h ough hem in he poin ed e e ence. The ools o s udy which a e used he e ha e
been published in ano he ounda ional wo k in Sinha [5].
5. Design o expe imen
5.1. Pipeline o ime se ies da a
Fo he case o ime se ies da a, in e ac ions among he con ibu ing ac o s a e s udied
by compa ing iple s o old-changes a single ime poin s. The p odecu e begins wi h
he gene a ion o dis ibu ion a ound measu emen s a single ime poin s wi h added
noise is done o es ima e he indices. A dis ibu ion is gene a ed o he old changes
a single ime poin s. Then o e e y gene, he e is a ec o o alues ep esen ing old
changes as well as de ia ions in old changes o di e en ime poin s and du a ions
be ween ime poin s, espec i ely. Nex a lis ing o all Cn
kcombina ions o knumbe
o genes om a o al o ngenes is gene a ed. kis ≥2 and ≤(n−1). Each o he com-
bina ion o o de k ep esen s a unique se o in e ac ion be ween he in ol ed gene ic
ac o s. A e his, he da ase s a e combined in a speci ed o ma which go as inpu
as pe he equi emen o a pa icula sensi i i y analysis me hod. Thus o each p h
combina ion in Cn
kcombina ions, he da ase is p epa ed in he equi ed o ma om
he dis ibu ions o wo sepa a e cases which ha e been discussed abo e. (See .R code
in mainSc ip -1-1.R). A e he da a has been ans o med, ec o ized p og amming
is employed o densi y based sensi i i y analysis and looping is employed o a i-
ance based sensi i i y analysis o compu e he equi ed sensi i i y indices o each o
he pcombina ions. This p ocedu e is done o di e en kinds o sensi i i y analysis
me hods.
4
A e he abo e sensi i i y indices ha e been s o ed o each o he p h combina-
ion, he nex s ep in he design o expe imen is conduc ed. Since he e is only one
eco ding o sensi i i y index pe combina ion, each combina ion o ms a aining ex-
ample which is allo ed a aining index and he sensi i i y indices o he indi idual
gene ic ac o s o m he aining example. Thus he e a e Cn
k aining examples o k h
o de in e ac ion. Using his aining se SVMRank
lea n Joachims [3] is used o gene a e a
model on de aul alue C alue o 20. In he cu en expe imen on oy model C alue
has no been unned. The aining se helps in he gene a ion o he model as he di -
e en gene combina ions a e numbe ed in o de which a e used as ank indices. The
model is hen used o gene a e sco e on he obse a ions in he es ing se using he
SV MRank
classi y Joachims [3]. No e ha due o a ailabili y o only one example pe com-
bina ion, a e he model has been buil , he same aining da a is used as es da a o
gene a es he sco es. This p ocedu e is execu ed o each and e e y sensi i i y analysis
me hod. This is ollowed by so ing o hese sco es along wi h he ank indices (i.e he
aining indices) al eady assigned o he gene combina ions. The end esul is a so ed
o de o he gene combina ions based on he anking sco e lea ned by he SV MRank
algo i hm. Finally, his en i e p ocedu e is compu ed o sensi i i y indices gene a ed
o each and e e y old change a ime poin and de ia ions in old change a di e en
du a ions. Obse ing he changing ank o a pa icula combina ion a di e en imes
and di e en ime pe iods will e eal how a combina ion is beha ing.
No e ha he ollowing is he o de in which he iles should be execu ed in R, in
o de , o ob aining he desi ed esul s (No e ha he code will no be explained he e) - •
use sou ce(”mainSc ip -1-1.R”) wi h a gumen s o Dynamic da a •sou ce(”SVMRank-
Resul s-D.R”), o ank he in e ac ions (again his needs o be done sepa a ely o
di e en kinds o SA me hods), •use sou ce(”Combine-Time- iles.R”), i compu -
ing indices sepa a ely ia p e ious ile, •sou ce(”So -n-Plo -D.R”) o so he in e -
ac ions. No e ha he so ing is chages he in e ac ion anking in ime. Thus •use
sou ce(”In e ac ion-P io i y-In ime.R”) o ind he p io i ized anking o each and e -
e y in e ac ion o e he di e en ime poin s and inally •use sou ce(”P in -Ranking-
AND-In e ac ion-Rank.R”) o p in indi idual anking o he equi ed inpu ac o wi h
o he in e ac ion ac o s.
6. Resul s & Discussion
6.1. Time se ies da a by Guj al and MacBea h [1]
NOTE - Ranking was assigned on sco es ha we e so ed in DECREASING alues.
So, 1 was assigned o highes sco e and ice e sa.
Resul s o he 3 d o de in e ac ions a e p esen ed he e. The esul s i s discuss
he beha iou o in e ac ions ac oss he snapsho s o ime using he compu ed sensi-
i i ies on old change measu emen s pe ime snapsho . The analysis was done us-
ing 4 di e en sensi i i y indices. Ou o he 71C3combina ions, I conside /p esen
only hose combina ions ha show a anking wi hin i s 10,000 ou o 57,155. This
choice is libe al and biologis s/oncologis s can ha e a mo e s ic e choice as pe need.
Two obse a ions a e made, • he anking o a pa icula combina ion is conse ed (i.e
5
wi hin he 10,000 ange) in a pa icula ime poin o in he ea ly phase o la e phase
o WNT3A s imula ion, ac oss he majo i y o he ou sensi i i y me hods, which is a
s ic c i e ia o assessmen o • he anking o a pa icula combina ion is conse ed
ac oss ime poin s/phase (i.e hey a e wi hin he 10,000 ange) and he majo i y o he
ou sensi i i y me hods, which is elaxed c i e ia o assessmen . Applying his il e
helps e eal impo an combina ions o in e es ha migh be wo king syne gis ically
a a highe o de le el in he cell.
Rega ding echnical poin s o implemen a ion, he ankings we e gene a ed wi h-
ou scaling/no malizing he ime se ies da a p o ided by Guj al and MacBea h [1].
Fo es ima ing he sensi i i y indices, a small gaussian dis ibu ion using he unc ion
no m ha gene a es a ec o o no mally dis ibu ed andom a iables gi en a ec o
leng h n (he e 9, he 10 h one is he mean/ eco ded gene egula ion i sel ), a popula ion
mean µand popula ion s anda d de ia ion σ. The syn ax o using no m is as ollows:
no m(n, mean, sd). Fu he , I use he ji e un ion o add a li le bi o noise o he
da a. This helps o see i he gene a ed ankings a e obus o no .
6.2. Enume a ion and anking o 2415 DIXDC1-X-X combina ions
om Guj al and MacBea h [1]
In he supplemen a y sec ion, I p esen ou iles, each con aining he ankings o 3 d
o de combina ions, ha wa y in ime (shown o 5 ime poin s). Each ile ep esen s
he ankings compu ed using a pa icula sensi i i y me hod. The changing ankings
in ime o a pa icula combina ion ep esen s he impo ance o con ibu ion/ ole ha
combina ion plays in he cell s imula ed wi h WNT3A. The sensi i i y me hods used
a e Hilbe Schmid Independence C i e ion indices (HSIC) indices (wi h b and linea
ke nel in Da Veiga [6]) and Sobol indicies (wi h 2002 implemen a ion in Sal elli [7] and
ma inez implemen a ion in Ma inez [8] and Baudin e al. [9]).
6.3. Conse ed machine lea ning ankings o es ed DIXDC1-X-X
combina ions
A o al o 2415, 3 d o de combina ions in ol ing DIXDC1 we e ob ained om a ull
se o 71C3= 57155 combina ions. Fu he , om his selec ed se , using he abo e c i-
e ia o conse ed ankings, I epo / abula e he meaning ul combina ions ha migh
be wo king syne gis ically. Tables 2, 3 and 4 show he ankings o he same combi-
na ions as in able 1, bu using b ke nel o HSIC, 2002 implemen a ion o SOBOL
and ma inez implemen a ion o SOBOL, espec i ely. As one allies he ankings o
ac oss hese ables o a pa icula combina ion, one inds ha he ole o he combina-
ion o in e es is conse ed. This conse a ion poin s o he exis ence o he biological
syne gy, whe he he combina ion has been es ed o unexplo ed/un es ed.
6.3.1. Examining he beha iou o GSK3-DIXDC1-X combina ions
Ma in e al. [10] p opose ha a e missense single-nucleo ide a ian s (SNVs) in
DIXDC1 con ibu e o psychia ic pa hogenesis by educing spine and glu ama e gic
synapse densi y downs eam o GSK3 in he WNT/β-ca enin pa hway. Looking a he
6
RANKING @ iUSING HSIC - LINEAR
3 d o de comb. 1 3 6 12 24 3 d o de comb. 1 3 6 12 24
APC-DIXDC1-WNT2B 89 27000 33475 27891 27710 DIXDC1-NKD1-SENP2 139 26878 5252 13422 20937
DIXDC1-NKD1-TLE2 211 181 25309 23711 748 DIXDC1-NKD1-TCF7L1 239 17174 2661 14197 5839
DIXDC1-FOXN1-FBXW4 330 3748 17556 12016 30746 DIXDC1-NKD1-PPP2CA 440 13162 40123 35144 6197
CCND1-CTBP1-DIXDC1 516 56574 53031 16545 48176 DIXDC1-PITX2-SENP2 526 28707 7274 5676 35235
DIXDC1-FOXN1-TLE2 581 740 1891 12323 28293 DIXDC1-FOXN1-FZD8 584 8409 1800 17070 5733
DIXDC1-PITX2-SFRP4 614 29602 6543 3868 43507 DIXDC1-PORCN-WNT4 690 39847 12582 10499 56262
DIXDC1-FSHB-LEF1 777 45272 10940 6689 22555 DIXDC1-NKD1-WNT2 883 442 1751 18827 1642
DIXDC1-FOXN1-KREMEN1 939 687 5376 7847 13303 DIXDC1-FZD2-LEF1 942 12211 3020 42787 29981
DIXDC1-LRP5-SENP2 1098 18807 1510 3942 4609 DIXDC1-FZD2-TCF7L1 1100 22783 49446 23638 20089
DIXDC1-FGF4-FBXW4 1142 8123 30879 12840 50692 DIXDC1-FZD2-SENP2 1148 28328 6949 7791 20834
DIXDC1-WNT3-WNT4 1279 51438 14477 19803 17251 DIXDC1-JUN-FBXW4 1340 27624 17009 49472 50306
DIXDC1-JUN-TCF7L1 1397 18158 39442 41838 15514 DIXDC1-FOXN1-FRZB 1442 1877 4968 4749 2791
DIXDC1-FZD2-FZD8 1466 11545 29932 40243 14229 DIXDC1-FZD2-FZD7 1473 21462 19307 23718 22870
APC-DIXDC1-FRZB 1488 36338 55199 25861 797 DIXDC1-FOXN1-SENP2 1491 2077 4322 6058 1110
DIXDC1-PORCN-SENP2 1529 21963 6981 10680 50015 DIXDC1-FGF4-FRAT1 1533 9050 41138 51810 43824
DIXDC1-NKD1-WNT4 1536 13509 3143 4994 28564 DIXDC1-FZD2-WNT4 1576 35367 3250 12254 41951
DIXDC1-GSK3B-SLC9A3R1 1609 31242 3865 16239 26807 DIXDC1-GSK3A-SENP2 1621 28519 557 27468 36407
DIXDC1-FZD2-KREMEN1 1727 6226 28247 11263 35521 DIXDC1-NKD1-RHOU 1798 6195 3765 22405 3157
DIXDC1-NKD1-WNT5A 1830 5103 33835 49403 2232 DIXDC1-FGF4-FOSL1 1834 22981 29680 27665 50757
DIXDC1-FGF4-TLE2 1838 19948 33519 25723 52981 DIXDC1-FGF4-FZD8 1912 23178 24551 54089 31538
APC-DIXDC1-SFRP4 1940 34105 56875 25938 15956 APC-DIXDC1-DKK1 1973 39613 14672 51391 14145
DIXDC1-JUN-KREMEN1 2010 2457 38608 53030 25504 DIXDC1-FZD2-TLE2 2059 1052 41611 34129 44387
DIXDC1-FOXN1-WNT4 2069 18260 5558 10405 1210 FZD5-DIXDC1-FRZB 2081 26083 51583 4776 41242
DIXDC1-LRP5-WNT4 2098 56736 1699 4505 8233 DIXDC1-NLK-WNT4 2128 13920 3978 2846 15403
DIXDC1-WNT1-WNT4 2134 8527 1926 11050 9192 DIXDC1-JUN-SENP2 2137 30487 37871 53712 15183
DIXDC1-NKD1-PPP2R1A 2140 5484 54992 25998 568 DIXDC1-FGF4-FZD1 2148 34299 35191 38859 49381
DIXDC1-FZD2-FBXW4 2156 27392 32655 28804 43752 DIXDC1-GSK3A-WNT4 2177 45494 1826 20781 48238
DIXDC1-JUN-SLC9A3R1 2235 15861 11040 56361 22586 DIXDC1-JUN-TLE2 2288 253 494 55465 49628
DIXDC1-FOXN1-WNT2 2324 510 6244 12086 918 DIXDC1-PORCN-FBXW4 2360 25666 16237 7265 54640
DIXDC1-TLE1-TLE2 2398 24851 22502 52222 23488 DIXDC1-JUN-WNT2 2424 1633 23267 35271 23259
DIXDC1-FZD2-LRP5 2550 15903 14969 51496 19500 CSNK1G1-DIXDC1-WNT2B 2602 9079 34225 44850 51306
FZD5-DIXDC1-SENP2 2634 37000 48018 1887 44271 DIXDC1-FGF4-SENP2 2635 18261 53316 27142 35362
APC-DIXDC1-TCF7L1 2672 33791 54110 6164 16187 DIXDC1-GSK3A-SLC9A3R1 2673 40171 11882 42208 52840
DIXDC1-NKD1-TCF7 2704 16324 46726 24262 6288 DIXDC1-SFRP1-WNT4 2827 56975 50212 3166 44324
DIXDC1-PITX2-WNT2B 2863 14619 3889 45440 40568 DIXDC1-FOXN1-SLC9A3R1 2905 17149 580 6704 6648
CSNK1G1-DIXDC1-SENP2 2907 45126 54761 32938 29362 DIXDC1-GSK3A-SFRP4 3011 7186 9197 19775 49994
DIXDC1-FGF4-TCF7L1 3076 32005 36386 8205 35936 DIXDC1-FZD2-WNT2B 3115 8791 13513 44897 31757
DIXDC1-PYGO1-WNT2 3118 7736 11350 8945 27577 DIXDC1-FZD2-SFRP4 3134 5020 36408 6731 42615
DIXDC1-FSHB-FZD1 3136 45375 11211 11425 29794 DIXDC1-PORCN-TLE2 3192 8903 21007 23935 55707
DIXDC1-PYGO1-TCF7L1 3193 33168 18183 17378 30931 DIXDC1-PITX2-WNT4 3214 52681 19702 7189 37575
FZD5-DIXDC1-WNT2B 3222 37056 32234 42255 42076 DIXDC1-FOXN1-PPP2CA 3235 4976 13715 8671 2172
CSNK1G1-DIXDC1-RHOU 3247 13611 55894 17887 29476 DIXDC1-FSHB-T 3255 34040 47003 6560 49035
DIXDC1-PORCN-WNT2B 3266 11238 38406 37800 51881 DIXDC1-DVL2-FRAT1 3310 15749 16154 12064 34806
DIXDC1-JUN-RHOU 3325 2215 36161 42538 1991 DIXDC1-FOXN1-LEF1 3327 3173 8059 15927 10884
DIXDC1-GSK3A-KREMEN1 3347 13841 2607 50326 30275 DIXDC1-SFRP1-FBXW4 3348 22994 35667 16096 50638
DIXDC1-FGF4-TCF7 3385 34777 40983 22775 42381 APC-DIXDC1-FBXW2 3395 2911 34269 1471 6570
DIXDC1-EP300-FBXW11 3401 6056 10476 24069 55750 DIXDC1-FGF4-WNT5A 3402 30477 40511 46509 49117
DIXDC1-SFRP1-TCF7 3404 44931 42751 37910 31320 DIXDC1-NLK-FBXW4 3436 6471 26909 5680 17650
CSNK1G1-DIXDC1-DKK1 3474 22358 26349 38523 54006 DIXDC1-GSK3A-WNT2 3514 7982 20770 47082 45891
FZD5-CCND3-DIXDC1 3536 349 4283 26959 12747 DIXDC1-JUN-WNT3A 3551 836 21850 41587 6942
DIXDC1-FZD2-PPP2CA 3662 17928 10686 40372 29250 DIXDC1-GSK3A-RHOU 3688 25193 1738 30131 17732
DIXDC1-FZD6-FZD8 3726 30855 3487 51102 3333 DIXDC1-FOXN1-SFRP4 3785 1242 4939 11642 2468
DIXDC1-FOXN1-FZD1 3799 13273 8362 12714 28800 DIXDC1-FOXN1-FZD7 3818 4807 3291 13093 46632
DIXDC1-FGF4-SLC9A3R1 3858 41464 33881 21954 50193 DIXDC1-FOXN1-WNT5A 3863 7743 18318 21775 11741
DIXDC1-PORCN-WNT5A 3885 26867 8379 47688 52084 DIXDC1-NKD1-WIF1 3909 12873 22358 12920 23739
DIXDC1-FGF4-WNT4 4006 46441 40742 22331 52314 DIXDC1-PORCN-RHOU 4036 27252 7449 17205 39479
DIXDC1-GSK3A-TCF7L1 4067 26243 14041 22033 41642 DIXDC1-FOXN1-WNT2B 4120 780 1909 4603 6598
DIXDC1-PITX2-PPP2CA 4123 13781 1911 14325 45522 DIXDC1-FZD2-TCF7 4146 31420 19458 30214 27951
DIXDC1-PORCN-SLC9A3R1 4147 35870 12879 23397 50086 DIXDC1-FOXN1-LRP6 4184 4399 11080 16729 11346
DIXDC1-DVL2-FOSL1 4189 23516 3806 16734 50139 DIXDC1-FZD2-WNT2 4199 3075 55905 23835 33613
DIXDC1-FGF4-LRP5 4209 32587 26371 42858 41494 DIXDC1-FOXN1-PPP2R1A 4318 4042 7718 10315 5136
CSNK1G1-DIXDC1-FRZB 4374 20252 52588 28893 38695 APC-DIXDC1-FOSL1 4389 42880 52076 6079 13090
DIXDC1-JUN-TLE1 4454 18781 16283 26133 14897 DIXDC1-GSK3A-TLE2 4469 19803 48789 49172 55138
Table 1: Rankings o DIXDC1-X-X. A lis o app oxima ely i s 125 combina ions wi h ankings below
10,000 ou o 57,155. SA - HSIC; Ke nel - linea
ables abo e, one inds he ollowing combina ions o membe s o GSK amily along
wi h DIXDC1, o be p ominen a 3 d o de le el - DIXDC1-GSK3B-SLC9A3R1,
DIXDC1-GSK3A-KREMEN1, DIXDC1-GSK3A-TCF7L1, DIXDC1-GSK3A-SENP2,
DIXDC1-GSK3A-WNT4, DIXDC1-GSK3A-SLC9A3R1, DIXDC1-GSK3A-SFRP4,
7
RANKING @ iUSING HSIC - RBF
3 d o de comb. 1 3 6 12 24 3 d o de comb. 1 3 6 12 24
APC-DIXDC1-WNT2B 33671 16882 4145 48106 51792 DIXDC1-NKD1-SENP2 24325 22750 54264 38554 4248
DIXDC1-NKD1-TLE2 22103 8452 55942 25492 11873 DIXDC1-NKD1-TCF7L1 32308 45794 57018 24322 3679
DIXDC1-FOXN1-FBXW4 3530 9085 27138 3878 80 DIXDC1-NKD1-PPP2CA 9807 43231 37477 30170 1078
CCND1-CTBP1-DIXDC1 43082 54629 13851 25493 5299 DIXDC1-PITX2-SENP2 3537 43865 15972 13329 19669
DIXDC1-FOXN1-TLE2 1845 16001 48828 19868 1211 DIXDC1-FOXN1-FZD8 2700 34651 54623 33036 17361
DIXDC1-PITX2-SFRP4 9005 33898 35036 1595 29334 DIXDC1-PORCN-WNT4 25202 25146 26100 53862 33842
DIXDC1-FSHB-LEF1 56469 45507 52727 16153 8570 DIXDC1-NKD1-WNT2 30452 9192 55932 6605 10010
DIXDC1-FOXN1-KREMEN1 3184 5794 52693 37317 689 DIXDC1-FZD2-LEF1 35664 4924 22855 3469 6648
DIXDC1-LRP5-SENP2 1777 23484 44827 123 12925 DIXDC1-FZD2-TCF7L1 22093 37245 28474 19140 2863
DIXDC1-FGF4-FBXW4 863 8394 9981 4999 2166 DIXDC1-FZD2-SENP2 11918 40028 27691 41589 5926
DIXDC1-WNT3-WNT4 23687 55063 42305 53552 6689 DIXDC1-JUN-FBXW4 53699 39669 27414 16988 3729
DIXDC1-JUN-TCF7L1 36423 32144 31736 45585 462 DIXDC1-FOXN1-FRZB 2525 19420 51785 5266 224
DIXDC1-FZD2-FZD8 12238 10132 30096 29586 5638 DIXDC1-FZD2-FZD7 20526 11029 56170 887 16741
APC-DIXDC1-FRZB 10225 33713 18843 30318 48974 DIXDC1-FOXN1-SENP2 1565 39282 50555 4197 2183
DIXDC1-PORCN-SENP2 16346 39480 19973 18502 14705 DIXDC1-FGF4-FRAT1 2503 5561 19946 26820 16773
DIXDC1-NKD1-WNT4 28297 20930 51455 19765 821 DIXDC1-FZD2-WNT4 16200 33727 42194 2888 3723
DIXDC1-GSK3B-SLC9A3R1 40658 33882 42168 6416 5904 DIXDC1-GSK3A-SENP2 407 29880 52868 49762 5769
DIXDC1-FZD2-KREMEN1 14683 17223 32337 21120 1723 DIXDC1-NKD1-RHOU 22817 19488 48855 52946 7640
DIXDC1-NKD1-WNT5A 50477 15744 20410 52735 35648 DIXDC1-FGF4-FOSL1 2494 21424 29421 5565 13873
DIXDC1-FGF4-TLE2 483 5164 27361 31117 107 DIXDC1-FGF4-FZD8 298 43502 31467 49346 4208
APC-DIXDC1-SFRP4 35041 36541 11687 4001 53042 APC-DIXDC1-DKK1 15397 35669 351 47431 19313
DIXDC1-JUN-KREMEN1 28857 3 41815 56574 3054 DIXDC1-FZD2-TLE2 27650 769 44018 38166 114
DIXDC1-FOXN1-WNT4 3943 26131 55172 7688 2054 FZD5-DIXDC1-FRZB 7782 18262 19011 49028 55000
DIXDC1-LRP5-WNT4 7502 57090 41500 5927 3494 DIXDC1-NLK-WNT4 5010 8900 42377 1999 3181
DIXDC1-WNT1-WNT4 8940 3055 44478 355 3113 DIXDC1-JUN-SENP2 14743 34149 32447 35142 1484
DIXDC1-NKD1-PPP2R1A 41282 2633 37452 52221 22216 DIXDC1-FGF4-FZD1 747 28163 2771 16612 5332
DIXDC1-FZD2-FBXW4 10826 17817 13933 14350 2675 DIXDC1-GSK3A-WNT4 1408 54188 56943 11999 14706
DIXDC1-JUN-SLC9A3R1 52675 33774 46150 40855 4391 DIXDC1-JUN-TLE2 20372 1335 37154 33910 5318
DIXDC1-FOXN1-WNT2 4715 14636 41748 5 92 DIXDC1-PORCN-FBXW4 17443 35486 7874 10595 38652
DIXDC1-TLE1-TLE2 47116 48849 22114 26437 1356 DIXDC1-JUN-WNT2 54748 2832 42019 31686 7633
DIXDC1-FZD2-LRP5 38335 7398 15968 15952 6915 CSNK1G1-DIXDC1-WNT2B 56105 5718 34204 36658 46240
FZD5-DIXDC1-SENP2 7671 36100 18300 18941 42529 DIXDC1-FGF4-SENP2 160 19260 11857 32192 2906
APC-DIXDC1-TCF7L1 12380 40622 3158 36294 44580 DIXDC1-GSK3A-SLC9A3R1 2313 39361 52671 23807 16817
DIXDC1-NKD1-TCF7 22420 28291 44348 38473 4381 DIXDC1-SFRP1-WNT4 33874 55995 36243 38745 9587
DIXDC1-PITX2-WNT2B 12649 21037 9654 4112 8993 DIXDC1-FOXN1-SLC9A3R1 5496 29137 51814 26182 1076
CSNK1G1-DIXDC1-SENP2 37857 43110 9454 11888 27966 DIXDC1-GSK3A-SFRP4 1515 4288 53430 32178 8501
DIXDC1-FGF4-TCF7L1 651 50224 24155 46787 4158 DIXDC1-FZD2-WNT2B 29750 42429 10691 1083 508
DIXDC1-PYGO1-WNT2 9260 4892 51202 277 17819 DIXDC1-FZD2-SFRP4 12606 2707 46976 3589 4712
DIXDC1-FSHB-FZD1 3527 44586 55840 4528 2895 DIXDC1-PORCN-TLE2 19616 669 29894 3284 37516
DIXDC1-PYGO1-TCF7L1 9179 35935 48383 28960 14143 DIXDC1-PITX2-WNT4 11062 47027 42885 4269 14148
FZD5-DIXDC1-WNT2B 23182 22191 7617 31293 49776 DIXDC1-FOXN1-PPP2CA 1796 26077 33448 2622 1308
CSNK1G1-DIXDC1-RHOU 49459 11518 16506 41618 49774 DIXDC1-FSHB-T 36455 36262 54691 1183 12572
DIXDC1-PORCN-WNT2B 20111 15273 9550 18377 30375 DIXDC1-DVL2-FRAT1 34751 15623 55443 44289 5640
DIXDC1-JUN-RHOU 18846 1396 22896 56027 5582 DIXDC1-FOXN1-LEF1 4484 22384 44563 30946 6976
DIXDC1-GSK3A-KREMEN1 962 5165 52201 49330 13895 DIXDC1-SFRP1-FBXW4 45118 28237 10152 6125 20898
DIXDC1-FGF4-TCF7 212 40331 3449 35829 42516 APC-DIXDC1-FBXW2 10263 2964 14162 56148 46075
DIXDC1-EP300-FBXW11 24668 2475 1975 54678 8438 DIXDC1-FGF4-WNT5A 4107 43702 11521 38540 15389
DIXDC1-SFRP1-TCF7 8030 45487 21797 52378 10376 DIXDC1-NLK-FBXW4 25837 3880 29684 25017 18802
CSNK1G1-DIXDC1-DKK1 26769 29764 1454 44361 36145 DIXDC1-GSK3A-WNT2 6700 15468 53440 14555 7349
FZD5-CCND3-DIXDC1 11879 28312 52076 14071 46337 DIXDC1-JUN-WNT3A 26524 53 54094 51456 1811
DIXDC1-FZD2-PPP2CA 8902 30326 5894 8118 11004 DIXDC1-GSK3A-RHOU 1189 22635 55336 44689 20684
DIXDC1-FZD6-FZD8 49470 13675 53674 51243 47473 DIXDC1-FOXN1-SFRP4 3331 12759 51727 22386 2313
DIXDC1-FOXN1-FZD1 1993 16416 32872 56 73 DIXDC1-FOXN1-FZD7 4124 10434 48541 5064 21094
DIXDC1-FGF4-SLC9A3R1 5138 30311 47799 27456 9771 DIXDC1-FOXN1-WNT5A 5575 34443 41139 40268 26945
DIXDC1-PORCN-WNT5A 17412 29192 9192 10144 42283 DIXDC1-NKD1-WIF1 44180 9421 57087 48747 10766
DIXDC1-FGF4-WNT4 313 50493 39435 43390 15890 DIXDC1-PORCN-RHOU 12463 7504 10181 47443 33854
DIXDC1-GSK3A-TCF7L1 1618 40131 51849 34033 22311 DIXDC1-FOXN1-WNT2B 4897 28389 42117 706 3398
DIXDC1-PITX2-PPP2CA 5166 50281 13595 5982 18374 DIXDC1-FZD2-TCF7 10913 27332 15382 32534 9573
DIXDC1-PORCN-SLC9A3R1 29598 31337 32266 1590 25940 DIXDC1-FOXN1-LRP6 11784 23013 33845 22671 7286
DIXDC1-DVL2-FOSL1 43944 24373 54411 4440 3516 DIXDC1-FZD2-WNT2 20495 10746 26583 29184 3097
DIXDC1-FGF4-LRP5 2094 38170 10348 51983 7277 DIXDC1-FOXN1-PPP2R1A 3585 17552 18249 8440 13079
CSNK1G1-DIXDC1-FRZB 40009 20796 7792 3587 52750 APC-DIXDC1-FOSL1 29898 50944 4006 7452 38509
DIXDC1-JUN-TLE1 38829 51316 25565 40475 1022 DIXDC1-GSK3A-TLE2 619 4353 47970 38190 7644
Table 2: Rankings o DIXDC1-X-X. A lis o app oxima ely i s 125 combina ions wi h ankings below
10,000 ou o 57,155. SA - HSIC; Ke nel - b
DIXDC1-GSK3A-WNT2, DIXDC1-GSK3A-RHOU and DIXDC1-GSK3A-TLE2. All
hese combina ions indica e he exis ence o a possible syne gy when hey ake a highe
ank in he lis o combina ions.
8
RANKING @ iUSING SOBOL - 2002
3 d o de comb. 1 3 6 12 24 3 d o de comb. 1 3 6 12 24
APC-DIXDC1-WNT2B 32686 46138 57032 49706 8604 DIXDC1-NKD1-SENP2 12200 40063 24628 25782 18022
DIXDC1-NKD1-TLE2 43632 33173 40815 48692 18613 DIXDC1-NKD1-TCF7L1 55683 3768 38514 52231 4444
DIXDC1-FOXN1-FBXW4 3908 42858 13043 142 51587 DIXDC1-NKD1-PPP2CA 13275 33550 23785 28183 10803
CCND1-CTBP1-DIXDC1 51559 45701 51922 55396 12393 DIXDC1-PITX2-SENP2 55978 6920 46363 55209 16814
DIXDC1-FOXN1-TLE2 862 48313 19636 847 30685 DIXDC1-FOXN1-FZD8 1805 11167 25446 13189 38746
DIXDC1-PITX2-SFRP4 46369 10535 43650 52909 13347 DIXDC1-PORCN-WNT4 52700 17940 45762 56841 2056
DIXDC1-FSHB-LEF1 48274 9621 43078 41675 11440 DIXDC1-NKD1-WNT2 2739 39551 16389 12555 40067
DIXDC1-FOXN1-KREMEN1 21482 50446 17603 1664 40258 DIXDC1-FZD2-LEF1 1088 23042 12774 26014 35884
DIXDC1-LRP5-SENP2 4268 28488 25270 8378 13292 DIXDC1-FZD2-TCF7L1 56033 13065 46115 48353 32433
DIXDC1-FGF4-FBXW4 55336 3744 38325 50113 22659 DIXDC1-FZD2-SENP2 6691 25178 18767 17941 39342
DIXDC1-WNT3-WNT4 46662 7426 56710 34574 35761 DIXDC1-JUN-FBXW4 23517 23502 15073 18409 44877
DIXDC1-JUN-TCF7L1 9143 45568 15142 2009 35636 DIXDC1-FOXN1-FRZB 7469 45639 21161 7194 29894
DIXDC1-FZD2-FZD8 56260 17140 40677 41871 25346 DIXDC1-FZD2-FZD7 897 39906 16491 15323 31948
APC-DIXDC1-FRZB 31034 40280 35412 35124 5166 DIXDC1-FOXN1-SENP2 49092 3697 41057 55136 27309
DIXDC1-PORCN-SENP2 34245 4241 41483 50058 10738 DIXDC1-FGF4-FRAT1 2172 8556 22888 20956 35669
DIXDC1-NKD1-WNT4 4313 56293 22786 21278 56181 DIXDC1-FZD2-WNT4 230 13998 10061 1865 31112
DIXDC1-GSK3B-SLC9A3R1 234 54581 21361 4437 35419 DIXDC1-GSK3A-SENP2 4187 45495 18577 15069 48321
DIXDC1-FZD2-KREMEN1 37975 14894 44042 43100 25518 DIXDC1-NKD1-RHOU 51754 30025 31933 35781 48497
DIXDC1-NKD1-WNT5A 52842 853 34383 35927 975 DIXDC1-FGF4-FOSL1 3396 43706 23582 7101 52388
DIXDC1-FGF4-TLE2 54285 6424 40061 52770 29144 DIXDC1-FGF4-FZD8 40380 33429 31354 35470 16312
APC-DIXDC1-SFRP4 15501 36469 4573 12207 49027 APC-DIXDC1-DKK1 28809 54348 55519 53961 4157
DIXDC1-JUN-KREMEN1 460 53163 11120 19183 46244 DIXDC1-FZD2-TLE2 44992 16577 34379 33577 22179
DIXDC1-FOXN1-WNT4 56220 46188 42283 53911 12529 FZD5-DIXDC1-FRZB 51905 1632 56983 53968 5137
DIXDC1-LRP5-WNT4 22389 29687 26166 18602 8466 DIXDC1-NLK-WNT4 16250 51618 16235 15399 35237
DIXDC1-WNT1-WNT4 45923 10872 37922 33117 17030 DIXDC1-JUN-SENP2 38065 7371 44233 41749 19679
DIXDC1-NKD1-PPP2R1A 43958 23448 33394 28989 46225 DIXDC1-FGF4-FZD1 44874 43035 30939 38627 8168
DIXDC1-FZD2-FBXW4 56232 25918 42123 46272 12936 DIXDC1-GSK3A-WNT4 1153 10495 17804 9290 36662
DIXDC1-JUN-SLC9A3R1 33623 33561 42103 38759 12207 DIXDC1-JUN-TLE2 7892 39524 19988 13521 40054
DIXDC1-FOXN1-WNT2 43535 35529 42565 47624 18417 DIXDC1-PORCN-FBXW4 1721 49990 10280 3777 54067
DIXDC1-TLE1-TLE2 45671 17341 43136 37364 19250 DIXDC1-JUN-WNT2 56245 48642 40270 44652 20598
DIXDC1-FZD2-LRP5 56074 33993 44384 31111 21236 CSNK1G1-DIXDC1-WNT2B 12114 7749 26029 14404 44639
FZD5-DIXDC1-SENP2 12548 45142 1799 1150 54604 DIXDC1-FGF4-SENP2 454 43789 15313 3448 36983
APC-DIXDC1-TCF7L1 38058 40213 34148 43547 5611 DIXDC1-GSK3A-SLC9A3R1 9860 10843 21802 13865 42962
DIXDC1-NKD1-TCF7 1474 53318 18628 4936 52772 DIXDC1-SFRP1-WNT4 182 13057 19225 8756 34550
DIXDC1-PITX2-WNT2B 3174 55687 15258 13757 29932 DIXDC1-FOXN1-SLC9A3R1 53240 14302 44216 57016 5570
CSNK1G1-DIXDC1-SENP2 41101 55342 49465 39012 8801 DIXDC1-GSK3A-SFRP4 945 4750 12057 2266 34917
DIXDC1-FGF4-TCF7L1 50862 18674 31836 42480 10593 DIXDC1-FZD2-WNT2B 56478 39042 43251 43795 29912
DIXDC1-PYGO1-WNT2 38631 6548 43841 56224 38207 DIXDC1-FZD2-SFRP4 921 31332 15052 10925 44257
DIXDC1-FSHB-FZD1 26998 49234 15449 5156 42294 DIXDC1-PORCN-TLE2 8703 44992 26681 8337 53434
DIXDC1-PYGO1-TCF7L1 2188 42426 19263 4130 25766 DIXDC1-PITX2-WNT4 44341 8459 33406 35610 21988
FZD5-DIXDC1-WNT2B 54948 13222 54779 55520 8127 DIXDC1-FOXN1-PPP2CA 55813 13913 43667 51754 13189
CSNK1G1-DIXDC1-RHOU 16058 1799 7780 18030 48278 DIXDC1-FSHB-T 13832 55402 22848 25333 31832
DIXDC1-PORCN-WNT2B 3373 21084 13572 18388 49569 DIXDC1-DVL2-FRAT1 1757 23783 11410 15776 43723
DIXDC1-JUN-RHOU 19039 49606 12978 15409 37376 DIXDC1-FOXN1-LEF1 35678 6740 39623 55489 17084
DIXDC1-GSK3A-KREMEN1 56097 50759 42458 41643 27236 DIXDC1-SFRP1-FBXW4 55949 41407 41264 47501 25268
DIXDC1-FGF4-TCF7 6315 38617 25338 14741 46743 APC-DIXDC1-FBXW2 14383 8045 12142 11236 52411
DIXDC1-EP300-FBXW11 16478 41314 19565 26955 35640 DIXDC1-FGF4-WNT5A 54426 18498 38052 43829 24212
DIXDC1-SFRP1-TCF7 890 1914 16315 5621 27382 DIXDC1-NLK-FBXW4 54866 7550 40448 43753 13270
CSNK1G1-DIXDC1-DKK1 5009 2538 5529 18100 16388 DIXDC1-GSK3A-WNT2 597 7535 13277 13073 47490
FZD5-CCND3-DIXDC1 3555 36661 15848 15568 15517 DIXDC1-JUN-WNT3A 642 31777 12679 15634 45593
DIXDC1-FZD2-PPP2CA 5808 37464 22448 10828 35992 DIXDC1-GSK3A-RHOU 54644 35360 40518 47979 9311
DIXDC1-FZD6-FZD8 56956 15247 44176 49716 7398 DIXDC1-FOXN1-SFRP4 53999 36905 42015 41308 11320
DIXDC1-FOXN1-FZD1 1478 52928 13983 8965 23821 DIXDC1-FOXN1-FZD7 50549 11423 33617 36938 24059
DIXDC1-FGF4-SLC9A3R1 803 49054 15124 7558 23915 DIXDC1-FOXN1-WNT5A 7919 48369 15784 27764 27632
DIXDC1-PORCN-WNT5A 952 7968 6431 9090 46718 DIXDC1-NKD1-WIF1 2783 6193 1919 15666 44738
DIXDC1-FGF4-WNT4 2727 38766 19126 13360 32955 DIXDC1-PORCN-RHOU 22917 52952 15739 7094 46487
DIXDC1-GSK3A-TCF7L1 55304 4458 37900 47670 20477 DIXDC1-FOXN1-WNT2B 12833 46485 21688 21438 30822
DIXDC1-PITX2-PPP2CA 53041 37364 46121 33605 10550 DIXDC1-FZD2-TCF7 1127 43943 11040 8787 25066
DIXDC1-PORCN-SLC9A3R1 55438 7194 46909 53393 3075 DIXDC1-FOXN1-LRP6 55653 44861 40676 56911 28411
DIXDC1-DVL2-FOSL1 13850 26222 9929 15760 22430 DIXDC1-FZD2-WNT2 674 18194 13987 13381 27396
DIXDC1-FGF4-LRP5 50687 4628 32622 28888 25725 DIXDC1-FOXN1-PPP2R1A 6911 39828 26802 5793 42038
CSNK1G1-DIXDC1-FRZB 9906 50249 14891 20119 39408 APC-DIXDC1-FOSL1 20176 3680 12346 13612 45427
DIXDC1-JUN-TLE1 47964 11280 42049 55138 21421 DIXDC1-GSK3A-TLE2 44093 27389 37086 47589 18303
Table 3: Rankings o DIXDC1-X-X. A lis o app oxima ely i s 125 combina ions wi h ankings below
10,000 ou o 57,155. SA - SOBOL; Implemen a ion - 2002
6.3.2. Examining he beha iou o CCND-DIXDC1-X combina ions
DIXDC1 is he human homolog o Coiled-coil0-DIX1 (CCD1), a ecen ly iden i ied
DIX domain con aining p o ein in zeb a ish. I is a posi i e egula o in he WNT sig-
naling pa hway unc ioning downs eam o WNT and ups eam o AXIN. Wang e al.
9
