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One of the most pivotal games of the 2020 college football season, which also is one of the biggest contests in ACC history, takes the spotlight Saturday night as No. 1 Clemson travels to South Bend, Indiana, to face No. 4 Notre Dame. It's only fitting that in the one year the Fighting Irish are full conference members, they help make league history as part of just the sixth-ever meeting between top-five opponents in ACC play. The good news for Notre Dame is that the lower-ranked team has won in four of the previous five occasions, though none of those involved the No. 1 team in the country. 

But the circumstances are more than historic for the ranking but also unique for the 2020 season we're working through, as Clemson will be without star quarterback Trevor Lawrence because of COVID-19 protocol after a positive test. Lawrence is expected to be cleared to be with his teammates on the sideline for the game, but he remains in the cardiac monitoring portion of his return and was ruled out of Saturday night's game after last week's come-from-behind win against Boston College

The circumstances will be just a little different this week for true freshman D.J. Uiagalelei when he heads on the road in primetime against a tougher defense. But it will also be important to see how Clemson's defense responds after getting lit up by the Eagles last week. This game has plenty of ramifications for both teams. Let's take a closer look at the storylines to follow before making some expert picks both straight up and against the spread. Odds via William Hill Sportsbook

Storylines

Clemson: For all the attention that was rightly placed on the absence of Lawrence, last week also exposed some depth and injury concerns for Clemson that might not be entirely shored up by kickoff on Saturday night. Starting linebacker James Skalski has been dealing with a groin issue and will be out, leaving the Tigers without one of their key defensive leaders for the second straight game. Fellow starting linebacker Mike Jones Jr. is questionable after missing the Boston College game and starting defensive tackle Tyler Davis' status is unknown as he works his way back from getting banged up for the second time this season. Those absences on defense, particularly in the front seven, are going to put a lot of pressure on freshmen defensive linemen Bryan Bresee and Myles Murphy, as well as linebackers Jake Venables and Baylon Spector going up against Notre Dame's stellar rushing attack. The Fighting Irish win by controlling games with their offensive line and the combination of Kyren Williams and Chris Tyree. Clemson has to force Ian Book into third-and-long situations and get off the field when they do, limiting the opportunities for Notre Dame to put together long, punishing drives that will wear down an already-thin Tigers defense. 

Notre Dame: Brian Kelly has been awfully chippy this week when questioned about whether Saturday night is a chance for Notre Dame to prove that it belongs as one of college football's elite programs. "We're 29-3 over our last 32 games" and "we've won 12 in a row" were refrains used often by the Fighting Irish coach with shrugs that might as well have screamed "I don't know what else you want from us." Notre Dame has proven, really since 2017, that it's leveled up in a big way with its strength and conditioning program getting overhauled, and the team's identity coming from player development and cycling out one set of juniors and senior starters for another on an annual basis. But while acknowledging that Kelly is right to believe his program belongs in the conversation, the media is also right to suggest that Saturday night is a huge opportunity for Notre Dame. There's not going to be a way to close the talent gap with a Clemson, Alabama, Ohio State or Georgia, but Kelly and the Fighting Irish can prove that talent acquisition is not the only path to victory in modern college football. 

Viewing information

Date: Saturday, Nov.  7 | Time: 7:30 p.m. ET
Location: Notre Dame Stadium -- South Bend, Indiana
TV: NBC * | Live stream: fuboTV (Try for free)

* USA Network will begin simulcasting the game at 7:55 p.m. as NBC will cut away for President-elect Joe Biden's speech. The broadcast will return to NBC once the speech is done.

Game prediction, picks

Earlier this season, we talked about Big Game Dabo and Clemson's trends to the under in regular-season matchups against fellow ranked teams. Unfortunately, I think the total has already been impacted by the absence of Lawrence. The score I'm working with right now is 31-24 Tigers, which would clear the posted total by a field goal. Notre Dame is operating with a ton of confidence right now -- not just as a team but a program as a whole -- and I think this is going to be a classic of a game, but winning these games is what Clemson does best. I'd be on the home dog if this spread was more than a touchdown, but I really think the Tigers win, so I'll lay the handful of points. Pick: Clemson -5.5 

Which college football picks can you make with confidence in Week 10, and which Pac-12 team will pull off a shocking upset? Visit SportsLine to see which teams will win and cover the spread -- all from a proven computer model that has returned over $4,100 in profit over the past four-plus seasons -- and find out.