Of all the matchups that cause the most anxiety for the lower-seeded teams, the dreaded 5-12 game has the most potential for an upset in the 2021 NCAA bracket. Since the NCAA Tournament bracket expanded in 1985, there have been 50 upsets by No. 12 seeds over No. 5 seeds, meaning the lower seed is 50-90, a 35.71 winning percentage. In the 35 NCAA Tournaments that 5-12 matchups existed, only five of them did not feature at least one 12-seed team winning in the first round. The most recent NCAA Tournament, in 2019, featured three No. 5 seeds going down in the opening round.

Will No 5 seeds Creighton, Colorado, Villanova or Tennessee go out in the first round of March Madness 2021? Or will 12-seeds fall short in March Madness 2021 for only the sixth time in history? Before making any 2021 March Madness bracket predictions, be sure to check out the 2021 NCAA Tournament bracket picks from the proven computer model at SportsLine

Their proven projection model has simulated every game in the tournament 10,000 times. It absolutely crushed its March Madness picks last tournament, beating nearly 90 percent of all CBS Sports brackets one year after finishing in the top five percent. The model also nailed 14 teams in the Sweet 16 last time.

It knows how to spot an upset as well. The same model has produced brackets that have nailed 15 of the 26 first-round upsets by double-digit seeds the last four tournaments. It also nailed massive upsets last time, including huge wins by No. 13 seed UC-Irvine over No. 4 seed Kansas State, No. 10 seed Florida over No. 7 seed Nevada, and No. 12 seed Oregon over No. 5 seed Wisconsin.

There's simply no reason to rely on luck when there's proven technology to help you dominate your 2021 March Madness picks. Now, the model has simulated every possible matchup in the 2021 NCAA Tournament and revealed its optimal bracket. You can only see it over at SportsLine.

Top 2021 March Madness bracket picks

One team set to disrupt 2021 March Madness brackets: No. 14 Colgate knocks off No. 3 Arkansas in the South Region. The Raiders played a conference-only schedule, but went 14-1 with their lone defeat coming by just two points.

Colgate's top three scorers are all seniors, and they've been in this position before. In the 2019 NCAA Tournament, No. 15 Colgate held a second-half lead over No. 2 Tennessee before the Vols pulled away. Guard Jordan Burns scored 32 points in that game, and now as a senior, he leads Colgate with 17 points per game and paced the Patriot League in assists. Arkansas struggled against dynamic playmakers like Missouri's Xavier Pinson and LSU's Javonte Smart, which is why the model likes the Raiders over the Razorbacks in the 2021 March Madness bracket.

Another team to back in your 2021 NCAA Tournament picks: The 12th-seeded Winthrop Eagles, who stun No. 5 Villanova in the first round of the South Region.

Villanova went 16-6 this season, but ran into Georgetown in the Big East Tournament quarterfinals, losing to the Hoyas 72-71. Despite that setback, the Wildcats won the Big East regular-season title on the back of Wooden Award finalist Jeremiah Robinson-Earl, who delivers 15.7 points and 8.3 rebounds per game. Winthrop was even better in 2020-21, losing only the back end of a doubleheader against UNC-Asheville on Jan. 29 en route to a 23-1 record and both the Big South regular-season and tournament titles.

Winthrop is 1-10 all time in the NCAA Tournament, only winning its first-round game in 2007 by shocking sixth-seeded Notre Dame the day before St. Patrick's Day. The SportsLine model likes Winthrop's chances to do even better Friday night and considers the Eagles one of the March Madness 2021 underdogs to watch.

How to make 2021 NCAA Tournament bracket predictions

SportsLine's model also has one region where you absolutely need to pick the No. 2 seed, and the Nos. 10 and 13 seeds both deliver huge first-round upsets. Nailing those picks could literally make or break your bracket. With the model's proven track record of calling bracket-busting upsets, you'll want to see which stunners it is calling this year before locking in any bracket picks.

So what's the optimal NCAA Tournament 2021 bracket? And which underdogs shock college basketball? Visit SportsLine now to see which double-digit seeds you can back with confidence, all from the model that's nailed 15 of the 26 double-digit seed upsets the past four years.