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Illumina, Inc. – ‘10-Q’ for 4/3/22 – ‘EX-101.DEF’

On:  Thursday, 5/5/22, at 4:09pm ET   ·   For:  4/3/22   ·   Accession #:  1110803-22-21   ·   File #:  1-35406

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  As Of               Filer                 Filing    For·On·As Docs:Size

 5/05/22  Illumina, Inc.                    10-Q        4/03/22   68:7.4M

Quarterly Report   —   Form 10-Q

Filing Table of Contents

Document/Exhibit                   Description                      Pages   Size 

 1: 10-Q        Quarterly Report                                    HTML   1.07M 
 2: EX-31.1     Certification -- §302 - SOA'02                      HTML     27K 
 3: EX-31.2     Certification -- §302 - SOA'02                      HTML     27K 
 4: EX-32.1     Certification -- §906 - SOA'02                      HTML     22K 
 5: EX-32.2     Certification -- §906 - SOA'02                      HTML     22K 
11: R1          Cover Page                                          HTML     73K 
12: R2          Condensed Consolidated Balance Sheets               HTML    121K 
13: R3          Condensed Consolidated Statements of Income         HTML    116K 
14: R4          Condensed Consolidated Statements of Comprehensive  HTML     41K 
                Income                                                           
15: R5          Condensed Consolidated Statements of Stockholders?  HTML    103K 
                Equity                                                           
16: R6          Condensed Consolidated Statements of Cash Flows     HTML    120K 
17: R7          Organization and Significant Accounting Policies    HTML     45K 
18: R8          Revenue                                             HTML     59K 
19: R9          Investments and Fair Value Measurements             HTML     91K 
20: R10         Debt                                                HTML     58K 
21: R11         Stockholders? Equity                                HTML     74K 
22: R12         Supplemental Balance Sheet Details                  HTML     58K 
23: R13         Legal Proceedings                                   HTML     34K 
24: R14         Income Taxes                                        HTML     26K 
25: R15         Segment Information                                 HTML     55K 
26: R16         Organization and Significant Accounting Policies    HTML     44K 
                (Policies)                                                       
27: R17         Organization and Significant Accounting Policies    HTML     30K 
                (Tables)                                                         
28: R18         Revenue (Tables)                                    HTML     53K 
29: R19         Investments and Fair Value Measurements (Tables)    HTML     85K 
30: R20         Debt (Tables)                                       HTML     42K 
31: R21         Stockholders? Equity (Tables)                       HTML     96K 
32: R22         Supplemental Balance Sheet Details (Tables)         HTML     69K 
33: R23         Segment Information (Tables)                        HTML     50K 
34: R24         Organization and Significant Accounting Policies -  HTML     44K 
                Narrative - Accounting Pronouncements Adopted in                 
                2022 (Details)                                                   
35: R25         Organization and Significant Accounting Policies -  HTML     30K 
                Summary of Calculation of Weighted Average Shares                
                used to Calculate Basic and Diluted Earnings Per                 
                Share (Details)                                                  
36: R26         Revenue - Disaggregation of Revenue (Details)       HTML     55K 
37: R27         Revenue - Remaining Performance Obligation          HTML     38K 
                (Details)                                                        
38: R28         Revenue - Narrative (Details)                       HTML     30K 
39: R29         Investments and Fair Value Measurements -           HTML     97K 
                Narrative (Details)                                              
40: R30         Investments and Fair Value Measurements -           HTML     26K 
                Marketable Equity Securities (Details)                           
41: R31         Investments and Fair Value Measurements - Fair      HTML     60K 
                Value Hierarchy of Assets and Liabilities                        
                (Details)                                                        
42: R32         Investments and Fair Value Measurements - Changes   HTML     36K 
                in Estimated Fair Value of Acquisition Related                   
                Contingent Consideration Liabilities (Details)                   
43: R33         Debt - Summary of Term Debt Obligations (Details)   HTML     44K 
44: R34         Debt - Narrative (Details)                          HTML    136K 
45: R35         Debt - Summary of Convertible Debt Obligations      HTML     40K 
                (Details)                                                        
46: R36         Stockholders? Equity - Narrative (Details)          HTML     24K 
47: R37         Stockholders? Equity - Summary of Restricted Stock  HTML     51K 
                Activity and Related Information (Details)                       
48: R38         Stockholders? Equity - Summary of Stock Option      HTML     43K 
                Activity Under all Stock Option Plans (Details)                  
49: R39         Stockholders? Equity - Narrative - Liability -      HTML     33K 
                Classified Award (Details)                                       
50: R40         Stockholders? Equity - Liability - Classified       HTML     31K 
                Awards (Details)                                                 
51: R41         Stockholders? Equity - Narrative - Employee Stock   HTML     29K 
                Purchase Plan (Details)                                          
52: R42         Stockholders? Equity - Narrative - Share            HTML     28K 
                Repurchases (Details)                                            
53: R43         Stockholders? Equity - Summary of Share-based       HTML     51K 
                Compensation Expense for all Stock Awards                        
                (Details)                                                        
54: R44         Stockholders? Equity- Summary of Assumptions Used   HTML     47K 
                to Estimate the Weighted Average Fair Value Per                  
                Share (Details)                                                  
55: R45         Supplemental Balance Sheet Details - Schedule of    HTML     28K 
                Accounts Receivable (Details)                                    
56: R46         Supplemental Balance Sheet Details - Summary of     HTML     33K 
                Inventory (Details)                                              
57: R47         Supplemental Balance Sheet Details - Summary of     HTML     36K 
                Accrued Liabilities (Details)                                    
58: R48         Supplemental Balance Sheet Details - Summary of     HTML     28K 
                Changes in Reserve for Product Warranties                        
                (Details)                                                        
59: R49         Supplemental Balance Sheet Details - Narrative -    HTML     28K 
                Warranties (Details)                                             
60: R50         Supplemental Balance Sheet Details - Narrative -    HTML     29K 
                Derivatives (Details)                                            
61: R51         Legal Proceedings (Details)                         HTML     33K 
62: R52         Income Taxes (Details)                              HTML     26K 
63: R53         Segment Information - Summary of Operating          HTML     51K 
                Performance and Assets by Segment (Details)                      
66: XML         IDEA XML File -- Filing Summary                      XML    120K 
64: XML         XBRL Instance -- ilmn-20220403_htm                   XML   1.62M 
65: EXCEL       IDEA Workbook of Financial Reports                  XLSX     79K 
 7: EX-101.CAL  XBRL Calculations -- ilmn-20220403_cal               XML    167K 
 8: EX-101.DEF  XBRL Definitions -- ilmn-20220403_def                XML    612K 
 9: EX-101.LAB  XBRL Labels -- ilmn-20220403_lab                     XML   1.44M 
10: EX-101.PRE  XBRL Presentations -- ilmn-20220403_pre              XML    876K 
 6: EX-101.SCH  XBRL Schema -- ilmn-20220403                         XSD    135K 
67: JSON        XBRL Instance as JSON Data -- MetaLinks              381±   544K 
68: ZIP         XBRL Zipped Folder -- 0001110803-22-000021-xbrl      Zip    267K 


‘EX-101.DEF’   —   XBRL Definitions — ilmn-20220403_def


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9 Subsequent Filings that Reference this Filing

  As Of               Filer                 Filing    For·On·As Docs:Size             Issuer                      Filing Agent

 5/05/23  Illumina, Inc.                    10-Q        4/02/23   67:7.1M
 2/07/23  Illumina, Inc.                    8-K:2,9     2/07/23   11:1.2M
 1/11/23  Illumina, Inc.                    8-K:2,9     1/09/23   13:332K
12/01/22  Illumina, Inc.                    424B2                  2:533K                                   Donnelley … Solutions/FA
11/29/22  Illumina, Inc.                    424B2                  1:500K                                   Donnelley … Solutions/FA
11/04/22  Illumina, Inc.                    10-Q       10/02/22   70:8.9M
11/03/22  Illumina, Inc.                    8-K:2,9    11/03/22   11:1.1M
 8/11/22  Illumina, Inc.                    10-Q        7/03/22   72:9M
 8/11/22  Illumina, Inc.                    8-K:2,9     8/11/22   11:1M


6 Previous Filings that this Filing References

  As Of               Filer                 Filing    For·On·As Docs:Size             Issuer                      Filing Agent

 2/18/22  Illumina, Inc.                    10-K        1/02/22  108:15M
 8/18/21  Illumina, Inc.                    8-K:1,2,8,9 8/18/21   12:686K                                   Cravath Swaine & … 01/FA
 4/28/21  Illumina, Inc.                    10-Q        4/04/21   62:6.5M
 1/02/20  Illumina, Inc.                    8-K:1,7,9   1/02/20   14:223K
 9/26/19  Illumina, Inc.                    8-K:1,9     9/25/19   13:218K
11/05/18  Illumina, Inc.                    8-K:1,5,8,910/31/18    4:705K
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